Publications by authors named "Martin J Edelman"

162 Publications

Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer.

Lung Cancer 2022 04 4;166:135-142. Epub 2022 Mar 4.

Institut du Cancer de Montpellier, Montpellier, France.

Introduction: Topotecan is approved as second-line treatment for small cell lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support disialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus irinotecan in this setting. We tested dinutuximab/irinotecan versus irinotecan or topotecan as second-line therapy in relapsed/refractory (RR) SCLC.

Materials And Methods: Patients with RR SCLC and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:2:1 to receive dinutuximab 16-17.5 mg/m intravenous (IV)/irinotecan 350 mg/m IV (day 1), irinotecan 350 mg/m IV (day 1), or topotecan 1.5 mg/m IV (days 1-5) in 21-day cycles. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR; complete response [CR] + partial response [PR]), and clinical benefit rate (CBR; CR + PR + stable disease). Safety/tolerability were also assessed.

Results: A total of 471 patients were randomized to dinutuximab/irinotecan (n = 187), irinotecan (n = 190), or topotecan (n = 94). Age, sex, performance status, prior therapies, and metastatic disease sites were similar between groups. Survival and response rates were not improved for patients receiving dinutuximab/irinotecan versus those receiving irinotecan or topotecan (median OS 6.9 vs 7.0 vs 7.4 months [p = 0.3132]; median PFS 3.5 vs 3.0 vs 3.4 months [p = 0.3482]; ORR confirmed 17.1% vs 18.9% vs 20.2% [p = 0.8043]; and CBR 67.4% vs 58.9% vs 68.1% [p = 0.0989]), respectively. Grade 3/4 adverse events (≥5% receiving dinutuximab/irinotecan) included neutropenia, anemia, diarrhea, and asthenia.

Conclusions: Dinutuximab/irinotecan treatment did not result in improved OS in RR SCLC versus irinotecan alone. Irinotecan administered every 21 days demonstrated comparable activity to topotecan administered daily × 5 every 21 days.

Clinicaltrials: gov Identifier. NCT03098030.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2022.03.003DOI Listing
April 2022

Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10 advanced non-small cell lung cancer.

J Immunother Cancer 2022 01;10(1)

Adaptimmune, Philadelphia, Pennsylvania, USA.

Background: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10 tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-003 was a phase I dose-escalation trial that aimed to evaluate the safety and antitumor activity of ADP-A2M10 in non-small cell lung cancer (NSCLC) (NCT02592577).

Methods: Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08-0.12×10 (dose group 1), 0.5-1.2×10 (dose group 2), and 1.2-15×10 (dose group 3/expansion) transduced cells.

Results: Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three patients received cells in dose group 1, dose group 2, and dose group 3/expansion, respectively. The most frequently reported grade ≥3 adverse events were lymphopenia (n=11), leukopenia (n=10), neutropenia (n=8), anemia (n=6), thrombocytopenia (n=5), and hyponatremia (n=5). Three patients presented with cytokine release syndrome (grades 1, 2, and 4, respectively). One patient received the highest dose of lymphodepletion (fludarabine 30 mg/m on days -5 to -2 and cyclophosphamide 1800 mg/m on days -5 to -4) prior to a second infusion of ADP-A2M10 and had a partial response, subsequently complicated by aplastic anemia and death. Responses included: partial response (after second infusion; one patient), stable disease (four patients), clinical or radiographic progressive disease (five patients), and not evaluable (one patient). ADP-A2M10 were detectable in peripheral blood and in tumor tissue. Peak persistence was higher in patients who received higher doses of ADP-A2M10.

Conclusions: ADP-A2M10 demonstrated an acceptable safety profile and no evidence of toxicity related to off-target binding or alloreactivity. There was persistence of ADP-A2M10 in peripheral blood as well as ADP-A2M10 trafficking into the tumor. Given the discovery that MAGE-A10 and MAGE-A4 expression frequently overlap, this clinical program closed as trials with SPEAR T cells targeting MAGE-A4 are ongoing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2021-003581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796260PMC
January 2022

Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology.

Cancer Treat Rev 2022 Mar 5;104:102337. Epub 2022 Jan 5.

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, United States; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address:

DNA repair vulnerabilities are present in a significant proportion of cancers. Specifically, germline alterations in DNA repair not only increase cancer risk but are associated with treatment response and clinical outcomes. The therapeutic landscape of cancer has rapidly evolved with the FDA approval of therapies that specifically target DNA repair vulnerabilities. The clinical success of synthetic lethality between BRCA deficiency and poly(ADP-ribose) polymerase (PARP) inhibition has been truly revolutionary. Defective mismatch repair has been validated as a predictor of response to immune checkpoint blockade associated with durable responses and long-term benefit in many cancer patients. Advances in next generation sequencing technologies and their decreasing cost have supported increased genetic profiling of tumors coupled with germline testing of cancer risk genes in patients. The clinical adoption of panel testing for germline assessment in high-risk individuals has generated a plethora of genetic data, particularly on DNA repair genes. Here, we highlight the therapeutic relevance of germline aberrations in DNA repair to identify patients eligible for precision treatments such as PARP inhibitors (PARPis), immune checkpoint blockade, chemotherapy, radiation therapy and combined treatment. We also discuss emerging mechanisms that regulate DNA repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2021.102337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016579PMC
March 2022

American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer.

Int J Radiat Oncol Biol Phys 2022 02 25;112(2):361-375. Epub 2021 Sep 25.

The University of Texas, M.D. Anderson Cancer Center, Houston, Texas.

Purpose: Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer.

Methods And Materials: A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles.

Results: Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases.

Conclusions: Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2021.09.022DOI Listing
February 2022

Harmonized Outcome Measures for Use in Non-Small Cell Lung Cancer Patient Registries and Clinical Practice.

J Natl Compr Canc Netw 2021 Aug 13. Epub 2021 Aug 13.

4OM1, Inc, Boston, Massachusetts.

Background: Lung cancer is the leading cause of cancer-related death in the United States and globally, and many questions exist about treatment options. Harmonizing data across registries and other data collection efforts would yield a robust data infrastructure to help address many research questions. The purpose of this project was to develop a minimum set of patient and clinician relevant harmonized outcome measures that can be collected in non-small cell lung cancer (NSCLC) patient registries and clinical practice.

Methods: Seventeen lung cancer registries and related efforts were identified and invited to submit outcome measures. Representatives from medical specialty societies, government agencies, health systems, health information technology groups, patient advocacy organizations, and industry formed a stakeholder panel to categorize the measures and harmonize definitions using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework (OMF).

Results: The panel reviewed 66 outcome measures and identified a minimum set of 8 broadly relevant measures in the OMF categories of patient survival, clinical response, events of interest, and resource utilization. The panel harmonized definitions for the 8 measures through in-person and virtual meetings. The panel did not reach consensus on 1 specific validated instrument for capturing patient-reported outcomes. The minimum set of harmonized outcome measures is broadly relevant to clinicians and patients and feasible to capture across NSCLC disease stages and treatment pathways. A pilot test of these measures would be useful to document the burden and value of the measures for research and in clinical practice.

Conclusions: By collecting the harmonized measures consistently, registries and other data collection systems could contribute to the development research infrastructure and learning health systems to support new research and improve patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2021.7021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036537PMC
August 2021

American Radium Society Appropriate Use Criteria: Radiation Therapy for Limited-Stage SCLC 2020.

J Thorac Oncol 2021 01 6;16(1):66-75. Epub 2020 Nov 6.

Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.

Introduction: Combined modality therapy with concurrent chemotherapy and radiation has long been the standard of care for limited-stage SCLC (LS-SCLC). However, there is controversy over best combined modality practices for LS-SCLC. To address these controversies, the American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) Committee have developed updated consensus guidelines for the treatment of LS-SCLC.

Methods: The ARS AUC are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for LS-SCLC. Agreement or consensus was defined as less than or equal to 3 rating points from the panel median. The consensus ratings and recommendations were then vetted by the ARS Executive Committee and subject to public comment before finalization.

Results: The ARS Thoracic AUC committee developed multiple consensus recommendations for LS-SCLC. There was strong consensus that patients with unresectable LS-SCLC should receive concurrent chemotherapy with radiation delivered either once or twice daily. For medically inoperable T1-T2N0 LS-SCLC, either concurrent chemoradiation or stereotactic body radiation followed by adjuvant chemotherapy is a reasonable treatment option. The panel continues to recommend whole-brain prophylactic cranial irradiation after response to chemoradiation for LS-SCLC. There was panel agreement that prophylactic cranial irradiation with hippocampal avoidance and programmed cell death protein-1/programmed death-ligand 1-directed immune therapy should not be routinely administered outside the context of clinical trials at this time.

Conclusions: The ARS Thoracic AUC Committee provide consensus recommendations for LS-SCLC that aim to provide a groundwork for multidisciplinary care and clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2020.10.020DOI Listing
January 2021

American Radium Society Appropriate Use Criteria on Radiation Therapy for Extensive-Stage SCLC.

J Thorac Oncol 2021 01 1;16(1):54-65. Epub 2020 Oct 1.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Introduction: The standard-of-care therapy for extensive-stage SCLC has recently changed with the results of two large randomized trials revealing improved survival with the addition of immunotherapy to first-line platinum or etoposide chemotherapy. This has led to a lack of clarity around the role of consolidative thoracic radiation and prophylactic cranial irradiation in the setting of chemoimmunotherapy.

Methods: The American Radium Society Appropriate Use Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with the application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for extensive-stage SCLC.

Results: Current evidence supports either prophylactic cranial irradiation or surveillance with magnetic resonance imaging every 3 months for patients without evidence of brain metastases. Patients with brain metastases should receive whole-brain radiation with a recommended dose of 30 Gy in 10 fractions. Consolidative thoracic radiation can be considered in selected cases with the recommended dose ranging from 30 to 54 Gy; this recommendation was driven by expert opinion owing to the limited strength of evidence, as clinical trials addressing this question remain ongoing.

Conclusions: Radiation therapy remains an integral component in the treatment paradigm for ES-SCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2020.09.013DOI Listing
January 2021

Benchmarks for Academic Oncology Faculty.

JCO Oncol Pract 2021 03 30;17(3):e440-e444. Epub 2020 Sep 30.

University of Nebraska Medical Center, Omaha, NE.

The role of clinical researchers is vital to cancer progress. The teaching, research, and leadership roles that academic oncologists hold need to be accounted for and appropriately compensated. National metrics are currently inexistent, but are necessary to move the oncology research field forward. Clinical research and routine clinical care must be harmoniously integrated without competing. This article reviews the national landscape of clinical cancer research and proposes a call for action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/OP.20.00020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462569PMC
March 2021

Resection following concurrent chemotherapy and high-dose radiation for stage IIIA non-small cell lung cancer.

J Thorac Cardiovasc Surg 2020 11 31;160(5):1331-1345.e1. Epub 2020 May 31.

Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Ga.

Objective: Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non-small cell lung cancer.

Methods: Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non-small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here.

Results: One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9).

Conclusions: Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2020.03.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702021PMC
November 2020

Biomarker Testing in Lung Cancer-What Does It Mean?

JAMA Netw Open 2020 06 1;3(6):e207171. Epub 2020 Jun 1.

Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.7171DOI Listing
June 2020

Prophylactic Cranial Irradiation for Small-Cell Lung Cancer: Time for a Reassessment.

Authors:
Martin J Edelman

Am Soc Clin Oncol Educ Book 2020 May;40:24-28

Fox Chase Cancer Center, Philadelphia, PA.

Prophylactic cranial irradiation (PCI) has been an accepted part of the management of both limited and small-cell lung cancer; however, the data that support its use in limited-stage disease is based on an analysis of trials done before currently accepted approaches to staging (i.e., brain MRI and/or PET scanning) were available. For extensive disease, data are available from two randomized studies that are in direct conflict. This article explores the basic rationale for PCI and the evidence indicating that it is time to readdress the question of its routine use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/EDBK_281041DOI Listing
May 2020

Alternative Multidisciplinary Management Options for Locally Advanced NSCLC During the Coronavirus Disease 2019 Global Pandemic.

J Thorac Oncol 2020 07 28;15(7):1137-1146. Epub 2020 Apr 28.

Department of Radiation Oncology, Emory University, Atlanta Veterans Affairs Health Care System, Atlanta, Georgia.

The coronavirus disease 2019 (COVID-19) pandemic is currently accelerating. Patients with locally advanced NSCLC (LA-NSCLC) may require treatment in locations where resources are limited, and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk of severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Although guiding data is scarce, we present an expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are the following: (1) reduce the number of visits to a health care facility, (2) reduce the risk of exposure to severe acute respiratory syndrome-coronavirus-2, (3) attenuate the immunocompromising effects of lung cancer therapies, and (4) provide effective oncologic therapy. Patients with resectable disease can be treated with definitive nonoperative management if surgical resources are limited or the risks of perioperative care are high. Nonoperative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules that may or may not affect long-term outcomes in an era in which immunotherapy is available. The order of treatments may be on the basis of patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually, cancer therapies may be withheld until symptoms have resolved with negative viral test results. The risk of severe treatment-related morbidity and mortality is increased for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2020.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194660PMC
July 2020

Population-Based Outcomes in NSCLC.

Authors:
Martin J Edelman

JNCI Cancer Spectr 2019 Sep 7;3(3):pkz022. Epub 2019 Jun 7.

Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pkz022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050018PMC
September 2019

The Underappreciated Role of the Humoral Immune System and B Cells in Tumorigenesis and Cancer Therapeutics: A Review.

Int J Radiat Oncol Biol Phys 2020 09 3;108(1):38-45. Epub 2020 Apr 3.

Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

The advent of immunotherapy has ushered in a new era in both cancer research and cancer treatment strategies. Published reviews have described potential mechanisms for therapeutic synergisms from the combination of radiation therapy and immunotherapy, largely overlooking the role of humoral immunity by only focusing on cellular immunity. Given that these 2 branches of the immune system are highly interdependent, in this review we detail both what has already been established regarding the role of humoral immunity in cancer and propose potential avenues that are ripe for further investigation and potential clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.03.022DOI Listing
September 2020

A War on Two Fronts: Cancer Care in the Time of COVID-19.

Ann Intern Med 2020 06 27;172(11):756-758. Epub 2020 Mar 27.

Fox Chase Cancer Center, Philadelphia, Pennsylvania (A.K., D.S.W., M.J.E., E.M.H., R.G.U., R.I.F.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7326/M20-1133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133056PMC
June 2020

New Therapies in Special Populations.

Authors:
Martin J Edelman

JCO Oncol Pract 2020 06 11;16(6):329-330. Epub 2020 Mar 11.

Fox Chase Cancer Center, Philadelphia, PA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/OP.20.00082DOI Listing
June 2020

Insurance Status is an Independent Predictor of Overall Survival in Patients With Stage III Non-small-cell Lung Cancer Treated With Curative Intent.

Clin Lung Cancer 2020 05 18;21(3):e130-e141. Epub 2019 Sep 18.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD. Electronic address:

Introduction: Population studies suggest an impact of insurance status on oncologic outcomes. We sought to explore this in a large single-institution cohort of patients with non-small-cell lung cancer (NSCLC).

Materials And Methods: We retrospectively analyzed 342 consecutive patients (January 2000 to December 2013) curatively treated for stage III NSCLC. Patients were categorized by insurance status as uninsured (U), Medicare/Medicaid + Veterans Affairs (M/M + VA), or Private (P). The χ test was utilized to compare categorical variables. The Kaplan-Meier approach and the Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR).

Results: Compared with M/M + VA patients, P insurance patients were more likely to be younger (P < .001), married (P < .001), Caucasian (P = .001), reside in higher median income zip codes (P < .001), have higher performance status (P < .001), and undergo consolidation chemotherapy (P < .001) and trimodality therapy (P < .001). Diagnosis to treatment was delayed > 30 days in U (67.3%), M/M + VA (68.1%), and P (52.6%) patients (P = .017). Compared with the M/M + VA and U cohorts, P insurance patients had improved OS (median/5-year: 30.7 months/34.2%, 19 months/17%, and 16.9 months/3.8%; P < .001) and FFR (median/5-year: 18.4 months/27.3%, 15.2 months/23.2%, and 11.4 months/4.8%; P = .012), respectively. On multivariate analysis, insurance status was an independent predictor for OS (P = .017) but not FFR.

Conclusion: Compared with U or M/M + VA patients, P insurance patients with stage III NSCLC were more likely to be optimally diagnosed and treated, resulting in a doubling of median OS for P versus U patients. Improved access to affordable health insurance is critical to combat inequities in access to care and has potential for improvements in cancer outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2019.08.009DOI Listing
May 2020

Outcomes of patients with disease recurrence after treatment for locally advanced non-small cell lung cancer detected by routine follow-up CT scans versus a symptom driven evaluation.

Lung Cancer 2019 09 9;135:16-20. Epub 2019 Jul 9.

Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address:

Objectives: The majority of patients with locally advanced non-small cell lung cancer (LANSCLC) will recur after receiving multimodal treatment with curative intent. Current guidelines recommend routine follow-up with computerized tomography (CT) scans, though minimal data exist on the utility of this approach nor has an optimal follow-up strategy to detect recurrence been defined. This study examined whether survival varied if relapse was detected with scheduled follow-up CT versus symptoms, and whether the pattern of recurrence affected these outcomes.

Materials And Methods: Single institution retrospective review of patients who had undergone definitive management of LANSCLC with chemoradiotherapy +/- surgical resection. Standard follow-up testing consisted of routine exam and chest CT beginning at every 3 months in the first year and decreasing to annually after the fifth year.

Results: 311 patients were assessed, of which 167 patients recurred and were evaluable. 104 progressions were detected by follow-up and 63 by symptoms. For the entire group, there was no difference in overall survival (OS) for those detected by scans vs. symptoms (7.6 vs. 6.1 months, p = 0.797). After excluding patients with oligometastatic (1-3) brain metastases (OBM), OS was superior in patients with scan detected relapse (7.5 vs. 3.4 months, p = 0.013).

Conclusions: Routine surveillance by CT chest detects more localized disease than symptom driven follow-up, though OS does not differ. This null result is largely driven by the favorable outcomes for patients with OBM who present symptomatically. A strategy of both chest and brain imaging could be considered and warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2019.07.009DOI Listing
September 2019

Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors.

Adv Ther 2019 10 13;36(10):2638-2678. Epub 2019 Aug 13.

Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

In the last few years, immunotherapy has transformed the way we treat solid tumors, including melanoma, lung, head neck, breast, renal, and bladder cancers. Durable responses and long-term survival benefit has been experienced by many cancer patients, with favorable toxicity profiles of immunotherapeutic agents relative to chemotherapy. Cures have become possible in some patients with metastatic disease. Additional approvals of immunotherapy drugs and in combination with other agents are anticipated in the near future. Multiple additional immunotherapy drugs are in earlier stages of clinical development, and their testing in additional tumor types is under way. Despite considerable early success and relatively fewer side effects, the majority of cancer patients do not respond to checkpoint inhibitors. Additionally, while the drugs are generally well tolerated, there is still the potential for significant, unpredictable and even fatal toxicity with these agents. Improved biomarkers may help to better select patients who are more likely to respond to these drugs. Two key biologically important predictive tissue biomarkers, specifically, PD-L1 and mismatch repair deficiency, have been FDA-approved in conjunction with the checkpoint inhibitor, pembrolizumab. Tumor mutation burden, another promising biomarker, is emerging in several tumor types, and may also soon receive approval. Finally, several other tissue and liquid biomarkers are emerging that could help guide single-agent immunotherapy and in combination with other agents. Of these, one promising investigational biomarker is alteration or deficiency in DNA damage response (DDR) pathways, with altered DDR observed in a broad spectrum of tumors. Here, we provide a critical overview of current, emerging, and investigational biomarkers in the context of response to immunotherapy in solid tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-019-01051-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778545PMC
October 2019

SWOG S1400C (NCT02154490)-A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy).

J Thorac Oncol 2019 10 11;14(10):1853-1859. Epub 2019 Jul 11.

Medical Oncology, Yale Cancer Center, New Haven, Connecticut.

Objective: Lung-MAP (SWOG S1400) is a master platform trial assessing targeted therapies in squamous NSCLC. The objective of study C (S1400C) was to evaluate the response rate to palbociclib, a cyclin-dependent kinase 4 and cyclin-dependent kinase 6 inhibitor, in patients with cell cycle gene abnormalities.

Methods: Patients with squamous NSCLC, a performance status of 0 to 2, and normal organ function who had progressed after at least one prior platinum-based chemotherapy with cyclin-dependent kinase 4 gene (CDK4) or cyclin D1 gene (CCND1), cyclin D2 gene (CCND2), or cyclin D3 gene (CCND3) amplifications on tumor specimens were eligible. The study was originally designed as a phase II/III trial comparing palbociclib with docetaxel, but it was modified to a single-arm phase II trial with the primary end point of response when immunotherapy was approved. If two or fewer responses were seen in the first 20 patients, then the study would cease enrollment.

Results: A total of 88 patients (9% of patients screened) were assigned to S1400C, and 53 patients enrolled (including 17 to receive docetaxel). One patient who had been registered to receive docetaxel was re-registered to receive palbociclib after progression while taking docetaxel. The frequencies of cell cycle gene alterations in the eligible patients taking palbociclib (n = 32) were as follows: CCND1, 81% (n = 26); CCND2, 9% (n = 3); CCND3, 6% (n = 2); and CDK4, 3% (n = 1). In all, 32 eligible patients received palbociclib. There were two partial responses (response rate 6% [95% confidence interval (CI): 0%-15%]), both with CCND1 amplification. Twelve patients had stable disease (38% [95% CI: 21%-54%]). The median progression-free survival was 1.7 months (95% CI: 1.6-2.9 months) and the median overall survival was 7.1 months (95% CI: 4.2-12.5).

Conclusion: Palbociclib as monotherapy failed to demonstrate the prespecified criteria for advancement to phase III testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2019.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764876PMC
October 2019

Hope-related goal cognitions and daily experiences of fatigue, pain, and functional concern among lung cancer patients.

Support Care Cancer 2020 Feb 1;28(2):827-835. Epub 2019 Jun 1.

Department of Psychology, University of New Mexico, Albuquerque, NM, USA.

Purpose: Cross-sectional research suggests that thinking about multiple ways to reach goals (hope pathways) and the belief that one can reach them (hope agency) may be adaptive for lung cancer patients. We examined the between-person and within-person associations among aspects of hope agency and pathways thinking, daily fatigue, pain, and functional concerns (e.g., sense of independence, usefulness) among lung cancer patients during active treatment.

Methods: Data from a daily diary study were used to examine relations among hope agency, hope pathways, fatigue, pain, and functional concern in 50 patients with advanced lung cancer. Participants were accrued from one outpatient cancer center and completed the study between 2014 and 2015.

Results: Adjusting for covariates and the previous day's symptoms or concern, patients who engaged in higher pathways thinking reported lower daily symptoms, whereas those who engaged in higher agency thinking reported less functional concern. Within-person increases in pathways thinking were associated with less daily fatigue, pain, and functional concern; within-person increases in agency thinking were associated with less daily fatigue and pain. Models examining symptoms and concerns as predictors of hope suggested within-person increases in functional concern and fatigue and pain were related to lower agency and pathways thinking the same day. Patients with higher fatigue and pain did not report lower agency or pathways thinking, but patients with more functional concern did.

Conclusions: Increases in hope pathways thinking may be associated with lower symptoms and better functioning in lung cancer patients. This suggests that it is important to determine the efficacy of interventions that emphasize the pathways the component of hope.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-019-04878-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885110PMC
February 2020

Differential Gene Expression in Erlotinib-Treated Fibroblasts.

Nurs Res 2019 Mar/Apr;68(2):110-126

Karen E. Wickersham, PhD, RN, was Assistant Professor, School of Nursing, University of Maryland, Baltimore; now Assistant Professor, University of South Carolina, College of Nursing, Columbia, South Carolina. Theresa K. Hodges, PhD, is Bioinformatics Analyst I, Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, Maryland. Martin J. Edelman, MD, was Director, Medical Thoracic Oncology, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland; now Professor and Chair, Department of Hematology/Oncology; Deputy Director, Cancer Center for Clinical Research; and G. Morris Dorrance Jr. Chair in Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Yang Song, PhD, is Bioinformatics Analyst II, Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, Maryland. Mintong Nan, BS, was Laboratory Research Technician, Department of Pain and Translational Symptom Science, University of Maryland, Baltimore, School of Nursing, Baltimore, Maryland. Susan G. Dorsey, PhD, RN, FAAN, is Professor and Chair, Department of Pain and Translational Symptom Science, University of Maryland, Baltimore, School of Nursing, Baltimore, Maryland; and PhD Student at the University of Maryland.

Background: Therapies targeting the epidermal growth factor receptor (EGFR) result in a painful rash, the most common and debilitating toxicity among patients with non-small cell lung cancer (NSCLC) who take EGFR tyrosine kinase inhibitor (TKI) therapy; however, predicting the development and the severity of the rash is difficult.

Objective: The aim of this study was to examine how erlotinib-an EGFR TKI that NSCLC patients take to stop or slow tumor growth-altered the transcriptome of dermal fibroblasts.

Methods: Dermal fibroblasts (ATCC PCS-201-012) were seeded in cell culture flasks, grown under standard conditions, and transferred to cell culture dishes. Cells were treated once daily for 3 days with erlotinib 100 nM (n = 5), erlotinib 1 μM (n = 5), vehicle 1 μM (dimethyl sulfoxide) (n = 5), or no treatment (n = 5). Total RNA was extracted using a standard TRIzol method and hybridized using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Raw intensities generated from the arrays were normalized using a Robust Multiarray Average method and analyzed using analysis of variance in Limma R software. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis to identify canonical or noncanonical signaling pathways enriched in this dataset.

Results: We selected genes for investigation based on their potential role in wound healing (AQP3), rash development (CCL2), fibroblast activation (PALLD), cancer and cancer progression (GDF-15, SLC7A11, MMP12, and DIRAS3), and cell cycle control (CDC6). We were able to validate four of these genes by both Western blot analysis and quantitative polymerase chain reaction (MMP12, CCL2, CDC6, and SLC7A11).

Discussion: If found predictive of rash in future studies using patient samples, our findings may help to identify those at risk for severe rash so that (a) the dose of EGFR TKI therapy may be adjusted; (b) additional treatments for the rash can be developed; and/or (c) precise, patient-centered interventions can be developed so that patients with cancer can better self-manage their rash and adhere to EGFR TKI treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NNR.0000000000000330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580303PMC
November 2019

A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited-stage small cell lung cancer in elderly patients versus younger patients.

Cancer 2019 02 21;125(3):382-390. Epub 2018 Oct 21.

Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.

Background: Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited-stage small cell lung cancer (LS-SCLC). Many patients with LS-SCLC are elderly with comorbidities.

Methods: Individual patient data were collected from 11 phase 2 or 3 trials for LS-SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression-free survival (PFS), the rate of severe adverse events, and off-treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients).

Results: Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18-1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03-1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently.

Conclusions: Elderly patients with LS-SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.31813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340765PMC
February 2019

Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non-small-cell Lung Cancer at Diagnosis.

Clin Lung Cancer 2019 01 24;20(1):e107-e114. Epub 2018 Sep 24.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD. Electronic address:

Background: We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non-small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases.

Materials And Methods: A retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed.

Results: The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009).

Conclusion: Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2018.09.014DOI Listing
January 2019

Case-control study of PD-1, PD-L1 and B7-H3 expression in lung cancer patients with and without human immunodeficiency virus (HIV) infection.

Lung Cancer 2018 09 26;123:87-90. Epub 2018 Jun 26.

Johns Hopkins School of Medicine, 301 Mason Lord Drive, Suite 4500, Baltimore, MD, 21224, USA. Electronic address:

Objective: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients.

Materials And Methods: We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3, and percent of tumor infiltrating immune cells (TII) expressing PD-1 and PD-L1. Positive expression was defined as >5%. Statistical analysis was performed using the non-parametric Mann-Whitney test and the chi-square test.

Results: PD-L1 expression on tumor cells was positive in 23% of cases and 46% of controls. B7-H3 expression on tumor cells was positive in 92% of cases and 69% of controls. PD-1 expression on TII was positive in 69% of cases and 54% of controls. PD-L1 expression on TII was positive in 31% of cases and 69% of controls. B7-H3 percent expression on tumor cells was significantly higher in cases vs. controls (median 90% vs 20%, p = 0.005), but there were no significant differences in percent expression of PD-L1 on tumor cells, PD-1 on TII or PD-L1 on TII.

Conclusion: HIV-infected lung cancer patients had significantly higher B7-H3 tumor expression compared to HIV-uninfected controls, with similar rates of tumor PD-L1 expression, as well as PD-1 and PD-L1 expression on TII. These results support inclusion of HIV-infected lung cancer patients in future immunotherapy trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2018.06.028DOI Listing
September 2018

Stereotactic Body Radiation Therapy for Operable Early-Stage Lung Cancer: Findings From the NRG Oncology RTOG 0618 Trial.

JAMA Oncol 2018 09;4(9):1263-1266

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas.

Importance: Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with medically inoperable early-stage lung cancer. However, its effectiveness in patients medically suitable for surgery is unclear.

Objective: To evaluate whether noninvasive SBRT delivered on an outpatient basis can safely eradicate lung cancer and cure selected patients with operable lung cancer, obviating the need for surgical resection.

Design, Setting, And Participants: Single-arm phase 2 NRG Oncology Radiation Therapy Oncology Group 0618 study enrolled patients from December 2007 to May 2010 with median follow-up of 48.1 months (range, 15.4-73.7 months). The setting was a multicenter North American academic and community practice cancer center consortium. Patients had operable biopsy-proven peripheral T1 to T2, N0, M0 non-small cell tumors no more than 5 cm in diameter, forced expiratory volume in 1 second (FEV1) and diffusing capacity greater than 35% predicted, arterial oxygen tension greater than 60 mm Hg, arterial carbon dioxide tension less than 50 mm Hg, and no severe medical problems. The data analysis was performed in October 2014.

Interventions: The SBRT prescription dose was 54 Gy delivered in 3 18-Gy fractions over 1.5 to 2.0 weeks.

Main Outcomes And Measures: Primary end point was primary tumor control, with survival, adverse events, and the incidence and outcome of surgical salvage as secondary end points.

Results: Of 33 patients accrued, 26 were evaluable (23 T1 and 3 T2 tumors; 15 [58%] male; median age, 72.5 [range, 54-88] years). Median FEV1 and diffusing capacity of the lung for carbon monoxide at enrollment were 72.5% (range, 38%-136%) and 68% (range, 22%-96%) of predicted, respectively. Only 1 patient had a primary tumor recurrence. Involved lobe failure, the other component defining local failure, did not occur in any patient, so the estimated 4-year primary tumor control and local control rate were both 96% (95% CI, 83%-100%). As per protocol guidelines, the single patient with local recurrence underwent salvage lobectomy 1.2 years after SBRT, complicated by a grade 4 cardiac arrhythmia. The 4-year estimates of disease-free and overall survival were 57% (95% CI, 36%-74%) and 56% (95% CI, 35%-73%), respectively. Median overall survival was 55.2 months (95% CI, 37.7 months to not reached). Protocol-specified treatment-related grade 3, 4, and 5 adverse events were reported in 2 (8%; 95% CI, 0.1%-25%), 0, and 0 patients, respectively.

Conclusions And Relevance: As given, SBRT appears to be associated with a high rate of primary tumor control, low treatment-related morbidity, and infrequent need for surgical salvage in patients with operable early-stage lung cancer.

Trial Registration: ClinicalTrials.gov Identifier: NCT00551369.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2018.1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117102PMC
September 2018

Do older patients with non-small cell lung cancer also benefit from first-line platinum-based doublet chemotherapy? Observations from a pooled analysis of 730 prospectively-treated patients (Alliance Study A151622).

J Geriatr Oncol 2018 09 27;9(5):501-506. Epub 2018 May 27.

Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address:

Objective: This study sought to define the role of first-line platinum-based doublet chemotherapy in older patients with non-small cell lung cancer (NSCLC).

Materials And Methods: We analyzed three first-line NSCLC trials: CALGB 9730, CALGB 30203, and CALGB 30801, which tested carboplatin and paclitaxel; carboplatin and gemcitabine; and carboplatin with either pemetrexed or gemcitabine, respectively. Overall survival was the primary endpoint. Age-based comparisons with a cutpoint of 65 years were performed with Cox proportional hazards models with adjustments for sex, tumor histology, cancer stage, chemotherapy, and smoking history and after stratifying by performance score. Secondary endpoints were grade 3-5 adverse events, chemotherapy cycles completed, and whether toxicity prompted chemotherapy discontinuation.

Results: 730 patients were included; 337 (46%) were 65+ years of age. No statistically significant difference in survival was observed for older (≥65) versus younger patients (HR = 1.096; 95% CI = (0.94, 1.28); p = 0.25). A trend emerged with increased odds of a grade 3-5 adverse event for patients ≥65 years versus <65 years (OR = 1.52; 95% CI = (0.99, 2.31); p = 0.05). The proportion of completed chemotherapy cycles was marginally lower in older patients (difference = -5%; 95% CI = (-9, 0.2); p = 0.06) for those ≥65 years versus <65 years, but no statistically significant difference occurred in the rate of chemotherapy discontinuation for toxicity (OR = 1.4; 95% CI = (0.85, 2.19); p = 0.21) for patients ≥65 years versus <65 years. A cutpoint of 70 years yielded similar results.

Conclusion: These findings support carboplatin doublet-based chemotherapy in select older patients with advanced NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgo.2018.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233872PMC
September 2018

Time-to-Treatment-Failure and Related Outcomes Among 1000+ Advanced Non-Small Cell Lung Cancer Patients: Comparisons Between Older Versus Younger Patients (Alliance A151711).

J Thorac Oncol 2018 07 30;13(7):996-1003. Epub 2018 Mar 30.

Mayo Clinic, Rochester, Minnesota. Electronic address:

Introduction: Time-to-treatment-failure (TTF) is the interval from chemotherapy initiation to premature discontinuation. We evaluated TTF based on age.

Methods: Pooled analyses were conducted with first-line chemotherapy trials for advanced NSCLC (CALGB 9730, 30203, and 30801). Comparisons among patients who were 65 years and older and 70 years and older were performed for TTF (primary endpoint), reasons for early chemotherapy cessation, grade 3+ adverse events, and overall survival.

Results: Among 1006 patients, 460 (46%) were older than 65 years of age. One hundred forty-five older patients (32% of this age cohort) completed all six planned chemotherapy cycles as did 170 (32%) younger patients. Median TTF was 2.9 months (95% confidence interval: 2.7- 3.2) in older patients and 3 months (95% confidence interval: 2.9-3.5) in younger patients; adjustment for performance status and stratification by chemotherapy by trial yielded no statistically significant age-based difference in TTF. However, reasons for early chemotherapy cessation differed between age groups (multivariate p = 0.004). Older patients were less likely to discontinue from cancer progression (41% versus 55%) and more likely from toxicity or patient choice (16% and 15%, respectively) compared to younger patients (13% and 6%, respectively). Older patients were more likely to experience grade 3+ adverse events (86% versus 79%) with no statistically significant difference in survival. An age cutpoint of 70+ years showed no difference in TTF, a lower trend of early cessation due to cancer progression, and somewhat shorter older patient survival.

Conclusions: TTF was comparable between older and younger patients; but different, age-based, and potentially modifiable reasons account for it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2018.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015776PMC
July 2018
-->