Publications by authors named "Silvia Novello"

266 Publications

How far we have come targeting BRAF-mutant non-small cell lung cancer (NSCLC).

Cancer Treat Rev 2021 Dec 31;103:102335. Epub 2021 Dec 31.

Univ Lyon, Claude Bernard Lyon 1 University, INSERM 1052, CNRS 5286, Centre Leon Berard, Cancer Research Center of Lyon, Lyon, France.

The advent of high-throughput sequencing has allowed to profoundly interrogate the molecular landscape of non-small cell lung cancer (NSCLC) in the last years. These findings constitute the opportunity to better stratify these patients in order to address specific treatments to well-defined oncogene-restricted subgroups. Among them, BRAF-mutated lung cancers represent around 4% of NSCLC, thus identifying a clinically relevant population that should be aptly managed. Pivotal phase II trials have demonstrated the efficacy of combinatorial treatment - dabrafenib plus trametinib, targeting both BRAF and MEK - for patients harboring V600E mutations, making this specific BRAF alteration a mandatory requirement in the genetic portrait of advanced non-squamous lung cancer patients. However, around half of BRAF+ NSCLC patients remain orphan of targeted approaches. Here we review the available evidence, mainly from a clinical perspective, of therapeutic strategies for both V600E and non-V600 patients, in terms of small molecule, immune checkpoint inhibitors and forthcoming integrated strategies. Looking at on-going clinical trials, a special attention is dedicated to emergent molecules and combinatorial strategies that not only will improve outcomes of classical V600E, but also will make concrete the chance of tailored treatments for the majority of BRAF-mutated patients.
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http://dx.doi.org/10.1016/j.ctrv.2021.102335DOI Listing
December 2021

Humoral immune response to SARS-CoV-2 in five different groups of individuals at different environmental and professional risk of infection.

Sci Rep 2021 12 30;11(1):24503. Epub 2021 Dec 30.

Department of Oncology at San Luigi Hospital, University of Torino, Regione Gonzole 10, 10043, Orbassano, Torino, Italy.

It is partially unknown whether the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection persists with time. To address this issue, we detected the presence of SARS-CoV-2 antibodies in different groups of individuals previously diagnosed with COVID-19 disease (group 1 and 2), or potentially exposed to SARS-CoV-2 infection (group 3 and 4), and in a representative group of individuals with limited environmental exposure to the virus due to lockdown restrictions (group 5). The primary outcome was specific anti-SARS-CoV-2 antibodies in the different groups assessed by qualitative and quantitative analysis at baseline, 3 and 6 months follow-up. The seroconversion rate at baseline test was 95% in group 1, 61% in group 2, 40% in group 3, 17% in group 4 and 3% in group 5. Multivariate logistic regression analysis revealed male gender, close COVID-19 contact and presence of COVID-19 related symptoms strongly associated with serological positivity. The percentage of positive individuals as assessed by the qualitative and quantitative tests was superimposable. At the quantitative test, the median level of SARS-CoV-2 antibody levels measured in positive cases retested at 6-months increased significantly from baseline. The study indicates that assessing antibody response to SARS-CoV-2 through qualitative and quantitative testing is a reliable disease surveillance tool.
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http://dx.doi.org/10.1038/s41598-021-04279-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718534PMC
December 2021

Targeting KRAS in NSCLC: Old Failures and New Options for "Non-G12c" Patients.

Cancers (Basel) 2021 Dec 16;13(24). Epub 2021 Dec 16.

Department of Oncology, University of Turin, AOU San Luigi Gonzaga, 10043 Turin, Italy.

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.G12C KRAS mutation positive patients is predicted to change soon. This review provides a comprehensive and critical overview of ongoing studies into NSCLC patients with KRAS mutations other than p.G12C and discusses future scenarios that will hopefully change the story of this disease.
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http://dx.doi.org/10.3390/cancers13246332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699276PMC
December 2021

RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability.

Drug Saf 2022 Jan 20;45(1):45-64. Epub 2021 Dec 20.

Department of Oncology, University of Turin, A.O.U. San Luigi Gonzaga, Turin, Italy.

Introduction: RELAY was a global, double-blind, placebo-controlled phase III study that demonstrated superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus placebo plus erlotinib (PBO + ERL) in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) mutation-positive, metastatic non-small-cell lung cancer (NSCLC).

Objective: This article provides an in-depth analysis of the safety profile of RAM + ERL versus PBO + ERL observed in RELAY.

Methods: Eligible patients met these criteria: stage IV NSCLC; EGFR exon 19 deletion or exon 21 substitution (L858R) mutation; Eastern Cooperative Oncology Group performance status 0 or 1; and no central nervous system metastases. Patients were randomized (1:1) to receive erlotinib 150 mg/day orally plus either ramucirumab 10 mg/kg intravenously or matching placebo once every 2 weeks, until disease progression or unacceptable toxicity. The primary endpoint was PFS. Safety was evaluated based on reported treatment-emergent adverse events (AEs) and clinical laboratory assessments.

Results: The safety population comprised 446 patients (221 in RAM+ERL arm; 225 in PBO + ERL arm) who received at least one dose of study drug between January 2016 and February 2018. The overall incidence of grade ≥ 3 AEs was higher with RAM + ERL than with PBO + ERL, primarily driven by grade 3 hypertension. Grade ≥ 3 dermatitis acneiform and diarrhea were also reported more frequently in the RAM + ERL arm. The increased incidence of AEs with RAM + ERL was easily detected through routine monitoring and managed through dose adjustments and appropriate supportive care.

Conclusion: This in-depth safety analysis from RELAY supports that RAM + ERL, irrespective of the increased incidence of AEs, does not affect a patient's ability to benefit from treatment.

Clinical Trial Registration Number: NCT02411448.
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http://dx.doi.org/10.1007/s40264-021-01127-2DOI Listing
January 2022

Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study.

Crit Rev Oncol Hematol 2022 Jan 20;169:103525. Epub 2021 Nov 20.

Department of Public Health, University of Naples Federico II, Naples, Italy. Electronic address:

Aims: The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients.

Methods: The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy.

Results: For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input parameters and ensuring that results would present a consistent behavior compared to the original ones.

Conclusions: our project, highlighted that the adoption of NGS allows to save personnel time dedicated to testing activities and to reduce the overall cost of testing per patient.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103525DOI Listing
January 2022

Epidermal growth factor receptor exon 20 insertion variants in non-small cell lung cancer patients.

Crit Rev Oncol Hematol 2022 Jan 18;169:103536. Epub 2021 Nov 18.

Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy. Electronic address:

Epidermal growth factor receptor (EGFR) exon 20 insertions occur rarely among different cancer types, with the highest frequency reported among non-small-cell lung cancer (NSCLC) patients, particularly adenocarcinomas (ADCs). Exon 20 insertions fall back in the tyrosine kinase domain, and can be clustered into two principal groups represented by in frame insertions and three to 21 bp (corresponding to 1-7 amino acids) duplications within amino acids 762 and 774. The identification of these alterations is key for an adequate management of NSCLC patients due to the possibility to treat these patients with specific targeted therapies. Next generation sequencing (NGS) technology, able to detect several hotspot gene mutations for different patients simultaneously, is the best detection approach due to its higher sensitivity and specificity compared to other techniques. Here we reviewed the principal biological characteristics, the main detection technologies and treatment options for NSCLC patients harbouring EGFR exon 20 insertions.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103536DOI Listing
January 2022

Major breakthroughs in lung cancer adjuvant treatment: Looking beyond the horizon.

Cancer Treat Rev 2021 Dec 18;101:102308. Epub 2021 Oct 18.

Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy. Electronic address:

We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease's recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.
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http://dx.doi.org/10.1016/j.ctrv.2021.102308DOI Listing
December 2021

Effectiveness of a Psychosocial Care Quality Improvement Strategy to Address Quality of Life in Patients With Cancer: The HuCare2 Stepped-Wedge Cluster Randomized Trial.

JAMA Netw Open 2021 10 1;4(10):e2128667. Epub 2021 Oct 1.

Medical Oncology Division, Department of Oncology, ASST of Cremona, Cremona, Italy.

Importance: Many patients with cancer who would benefit from psychosocial care do not receive it. Implementation strategies may favor the integration of psychosocial care into practice and improve patient outcomes.

Objective: To evaluate the effectiveness of the Humanization in Cancer Care (HuCare) Quality Improvement Strategy vs standard care as improvement of at least 1 of 2 domains (emotional or social function) of patient health-related quality of life at baseline and 3 months. A key secondary aim included investigation of the long-term effect.

Design, Setting, And Participants: HuCare2 was a multicenter, incomplete, stepped-wedge cluster randomized clinical trial, conducted from May 30, 2016, to August 28, 2019, in three 5-center clusters of cancer centers representative of hospital size and geographic location in Italy. The study was divided into 5 equally spaced epochs. Implementation sequence was defined by a blinded statistician; the nature of the intervention precluded blinding for clinical staff. Participants included consecutive adult outpatients with newly diagnosed cancer of any type and stage starting medical cancer treatment.

Interventions: The HuCare Quality Improvement Strategy comprised (1) clinician communication training, (2) on-site visits for context analysis and problem-solving, and (3) implementation of 6 evidence-based recommendations.

Main Outcomes And Measures: The primary outcome was the difference between the means of changes of individual scores in emotional or social functions of health-related quality of life detected at baseline and 3-month follow-up (within each group) and during the postintervention epoch compared with control periods (between groups). Long-term effect of the intervention (at 12 months) was assessed as a secondary outcome. Intention-to-treat analysis was used.

Results: A total of 762 patients (475 [62.3%] women) were enrolled (400 HuCare Quality Improvement Strategy and 362 usual care); mean (SD) age was 61.4 (13.1) years. The HuCare Quality Improvement Strategy significantly improved emotional function during treatment (odds ratio [OR], 1.13; 95% CI, 1.04-1.22; P = .008) but not social function (OR, 0.99; 95% CI, 0.89-1.09; P = .80). Effect on emotional function persisted at 12 months (OR, 1.05; 95% CI, 1.00-1.10; P = .04).

Conclusions And Relevance: In this trial, the HuCare Quality Improvement Strategy significantly improved the emotional function aspect of health-related quality of life during cancer treatment and at 12 months, indicating a change in clinician behavior and in ward organization. These findings support the need for strategies to introduce psychosocial care; however, more research is needed on factors that may maximize the effects.

Trial Registration: ClinicalTrials.gov Identifier: NCT03008993.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.28667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517739PMC
October 2021

Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1-Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042.

JTO Clin Res Rep 2021 Aug 1;2(8):100205. Epub 2021 Jul 1.

State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China.

Introduction: We retrospectively evaluated outcomes in patients with programmed death-ligand 1 (PD-L1)-positive non-small-cell lung cancer (NSCLC) to determine whether baseline (i.e., at study enrollment) brain metastases were associated with the efficacy of pembrolizumab versus chemotherapy.

Methods: We pooled data for patients with previously treated or untreated PD-L1‒positive (tumor proportion score [TPS], ≥1%) advanced or metastatic NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894). Patients received pembrolizumab (2 mg/kg, 10 mg/kg, or 200 mg every 3 wk or 10 mg/kg every 2 wk); chemotherapy was a comparator in all studies except KEYNOTE-001. All studies included patients with previously treated, stable brain metastases.

Results: A total of 3170 patients were included, 293 (9.2%) with and 2877 (90.8%) without baseline brain metastases; median (range) follow-up at data cutoff was 12.9 (0.1‒43.7) months. Pembrolizumab improved overall survival versus chemotherapy in patients with or without baseline brain metastases: benefit was seen in patients with PD-L1 TPS ≥50% (0.67 [95% confidence intervals (CI): 0.44‒1.02] and 0.66 [95% CI: 0.58‒0.76], respectively) and PD-L1 TPS ≥1% (0.83 [95% CI: 0.62‒1.10] and 0.78 [95% CI: 0.71‒0.85], respectively). Progression-free survival was improved, objective response rates were higher, and duration of response was longer with pembrolizumab versus chemotherapy regardless of brain metastasis status. The incidence of treatment-related adverse events with pembrolizumab versus chemotherapy was 66.3% versus 84.4% in patients with brain metastases and 67.2% versus 88.3% in those without.

Conclusions: Pembrolizumab monotherapy improved outcomes and was associated with fewer adverse events than chemotherapy in patients with treatment-naive and previously treated PD-L1‒positive advanced/metastatic NSCLC regardless of the presence of baseline treated, stable brain metastases.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474394PMC
August 2021

The Genomics of Young Lung Cancer: Comprehensive Tissue Genomic Analysis in Patients Under 40 With Lung Cancer.

JTO Clin Res Rep 2021 Jul 24;2(7):100194. Epub 2021 May 24.

Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Introduction: Lung adenocarcinomas in young patients (<40 y) are more likely to harbor targetable genomic alterations. This study aimed to determine whether the prevalence of targetable alterations is greater in young adults with lung carcinoma than in the overall lung cancer population. To reach this rare patient population, a web-based platform was used to recruit and enroll patients remotely.

Methods: In this prospective study, patients less than 40 years old at the time of primary lung cancer diagnosis with confirmed lung carcinoma were recruited from four global sites and remotely by means of a website. Genotyping data were collected, if available, or obtained by means of next-generation sequencing using the FoundationOne platform. The prevalence of targetable alterations was quantified across patients with advanced adenocarcinoma.

Results: Overall, 133 patients across five continents were included, 41% of whom enrolled online. The mean (SD) age at diagnosis was 34 (5.2) years; 79% had stage IV disease at diagnosis. Among patients with adenocarcinoma (n = 115), 112 entered the study with previous genomic testing results and 86 (77%) had targetable alterations in , , , , , or . Among those without targetable alterations, 14 received further testing and a targetable alteration was identified in eight (57%).

Conclusions: This study revealed the feasibility of using a web-based platform to recruit young patients with lung cancer and revealed that 94 of 112 (84%) with adenocarcinoma at any stage had targetable genomic alterations. Among patients with stage IV adenocarcinoma, 85% had a targetable alteration, which is higher than historical expectations for the general population.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474359PMC
July 2021

Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With -Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study.

JTO Clin Res Rep 2021 Feb 26;2(2):100114. Epub 2020 Oct 26.

Division of Oncology, Department of Medicine, Stanford University, Stanford, California.

Introduction: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets T790M and common -activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs.

Methods: Patients with advanced or metastatic -mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel).

Results: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07,  = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively).

Conclusions: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced -mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point.
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http://dx.doi.org/10.1016/j.jtocrr.2020.100114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474221PMC
February 2021

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images.

Cancers (Basel) 2021 Sep 10;13(18). Epub 2021 Sep 10.

Department of Medical Science, Division of Nuclear Medicine, University of Turin, 10126 Turin, Italy.

Lung cancer remains the leading cause of cancer-related death, and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the tumor immune microenvironment (TME). While the response in molecular targeted therapies relies on the presence of specific genetic alterations in tumor cells, accurate ICI biomarkers of response are lacking, and clinical outcome likely depends on multiple factors that are both host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in vitro/ex vivo analysis (ranging from conventional pathology to molecular biology) and in vivo analysis, where molecular imaging is showing an exponential growth and use due to technological advancements and to the new bioinformatics approaches applied to image analyses that allow the recovery of specific features in specific tumor subclones.
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http://dx.doi.org/10.3390/cancers13184543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464855PMC
September 2021

Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.

J Clin Oncol 2021 11 26;39(32):3633-3644. Epub 2021 Aug 26.

Toulouse University Hospital, Institut Universitaire du Cancer, Université Paul Sabatier, Toulouse, France.

Purpose: Squamous non-small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546).

Patients And Methods: Patients age ≥ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52-gene expression histology classifier (LP52).

Results: Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; = .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the LP52-positive population (median 14.0 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm.

Conclusion: In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.
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http://dx.doi.org/10.1200/JCO.20.03318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577684PMC
November 2021

Local for advanced, is this a paradox?

Transl Lung Cancer Res 2021 Jul;10(7):3324-3328

Medical Oncology Department, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.

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http://dx.doi.org/10.21037/tlcr-20-771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350073PMC
July 2021

Winds From the ORIENT: New Data to Inform RATIONAL Choice?

J Thorac Oncol 2021 09;16(9):1434-1436

Thoracic Oncology Unit, Department of Oncology, S. Luigi Gonzaga Hospital, University of Torino, Orbassano, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2021.07.003DOI Listing
September 2021

PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients.

Clin Lung Cancer 2021 Jul 20. Epub 2021 Jul 20.

Department of Cancer Medicine, Gustave Roussy, Villejuif, France; Université Paris-Saclay, Orsay, France.

Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival.
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http://dx.doi.org/10.1016/j.cllc.2021.07.008DOI Listing
July 2021

Exploring the immune-checkpoint inhibitors' efficacy/tolerability in special non-small cell lung cancer (NSCLC) populations: focus on steroids and autoimmune disease.

Transl Lung Cancer Res 2021 Jun;10(6):2876-2889

Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy.

The advent of immune-checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, both as monotherapy and in combination strategies, produced a paradigm change of the treatment algorithm for metastatic, non-oncogene addicted, non-small cell lung cancer (NSCLC) patients. Although the great efficacy and the optimal tolerability emerging from clinical studies has been confirmed for the majority of patients treated in the real-word scenario, however the potential activity and safety profile of these agents in uncommon NSCLC populations remains still controversial. Particularly, patients with previously diagnosed autoimmune disease or concomitant steroids treatment at the time of immunotherapy initiation represent two special subgroups of patients not unusual in the real-word practice, to whom the clinical implication of immune-checkpoint inhibitors administration is largely unknown. In this review we provided an updated literature overview, summarizing available evidence and reporting practical suggestions, which may guide physicians in their clinical management of these NSCLC sub-populations.
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http://dx.doi.org/10.21037/tlcr-20-635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264339PMC
June 2021

Repositioning PARP inhibitors in the treatment of thoracic malignancies.

Cancer Treat Rev 2021 Sep 7;99:102256. Epub 2021 Jul 7.

Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, TO, Italy. Electronic address:

The evaluation of the homologous recombination repair (HRR) status is emerging as a predictive tumor agnostic biomarker for poly (ADP-ribose) polymerase (PARP) inhibition across different tumor types and testing for HRR-signature is currently a developing area with promising therapeutic implications. Treatment with PARP inhibitors (PARPi) either as single agent or in combination with chemotherapy have shown so far limited activity in patients with thoracic malignancies. A deeper understanding of the biological background underlying HRR-deficient tumors, along with the recent advent of new effective targeted and immunotherapeutic agents, prompted the design of a new generation of clinical trials investigating novel PARPi-combinations in patients with lung cancer as well as malignant pleural mesothelioma. In this review we briefly summarize the biological basis of the DNA damage response pathway inhibition and provide an updated and detailed overview of clinical trials testing different PARPi-combinations strategies in patients with thoracic malignancies.
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http://dx.doi.org/10.1016/j.ctrv.2021.102256DOI Listing
September 2021

Benefits and Harms of Lung Cancer Screening by Chest Computed Tomography: A Systematic Review and Meta-Analysis.

J Clin Oncol 2021 08 2;39(23):2574-2585. Epub 2021 Jun 2.

Department of Oncology, San Luigi Hospital, University of Turin, Orbassano (TO), Italy.

Purpose: This meta-analysis aims to combine and analyze randomized clinical trials comparing computed tomography lung screening (CTLS) versus either no screening (NS) or chest x-ray (CXR) in subjects with cigarette smoking history, to provide a precise and reliable estimation of the benefits and harms associated with CTLS.

Materials And Methods: Data from all published randomized trials comparing CTLS versus either NS or CXR in a highly tobacco-exposed population were collected, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Subgroup analyses by comparator (NS or CXR) were performed. Pooled risk ratio (RR) and relative 95% CIs were calculated for dichotomous outcomes. The certainty of the evidence was assessed using the GRADE approach.

Results: Nine eligible trials (88,497 patients) were included. Pooled analysis showed that CTLS is associated with: a significant reduction of lung cancer-related mortality (overall RR, 0.87; 95% CI, 0.78 to 0.98; NS RR, 0.80; 95% CI, 0.69 to 0.92); a significant increase of early-stage tumors diagnosis (overall RR, 2.84; 95% CI 1.76 to 4.58; NS RR, 3.33; 95% CI, 2.27 to 4.89; CXR RR, 1.52; 95% CI, 1.04 to 2.23); a significant decrease of late-stage tumors diagnosis (overall RR, 0.75; 95% CI, 0.68 to 0.83; NS RR, 0.67; 95% CI, 0.56 to 0.80); a significant increase of resectability rate (NS RR, 2.57; 95% CI, 1.76 to 3.74); a nonsignificant reduction of all-cause mortality (overall RR, 0.99; 95% CI, 0.94 to 1.05); and a significant increase of overdiagnosis rate (NS, 38%; 95% CI, 14 to 63). The analysis of lung cancer-related mortality by sex revealed nonsignificant differences between men and women ( = .21; I-squared = 33.6%).

Conclusion: Despite there still being uncertainty about overdiagnosis estimate, this meta-analysis suggested that the CTLS benefits outweigh harms, in subjects with cigarette smoking history, ultimately supporting the systematic implementation of lung cancer screening worldwide.
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http://dx.doi.org/10.1200/JCO.20.02574DOI Listing
August 2021

Descriptive Comparative Analysis of Patients With Cancer Referring to the Emergency Department of an Italian University Hospital Across the Severe Acute Respiratory Syndrome Coronavirus 2 Waves.

JCO Oncol Pract 2021 12 6;17(12):e1887-e1894. Epub 2021 Jul 6.

Department of Oncology, University of Torino at San Luigi Gonzaga University Hospital, Orbassano, Italy.

Purpose: COVID-19 cancer patients (C19-CP) represent a population at high risk for mortality, whose clinical characteristics are still unknown in the second SARS-CoV-2 wave. The aim of this retrospective study was to compare epidemiology and clinical presentation of C19-CP referring to the emergency department (ED) of our institution (San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy), in a 3-week observation period of the first and second COVID-19 waves, starting from the introduction of the corresponding national lockdowns.

Methods: We retrieved ED admissions from March 9 to 29, 2020, for the first wave, and from October 24 to November 13, 2020, for the second wave. We collected clinical characteristics of consecutive patients with molecularly confirmed SARS-CoV-2 infection. We also considered untested or SARS-CoV-2-negative cancer patients referring to the ED in the reference time frames.

Results: C19-CP in the second wave exceeded those in the first wave despite the nonsignificant difference (39 of 576 8 of 163; = .5). Compared with nononcological patients, C19-CP were older (median age 70 years [interquartile range 61-77] 60 years [interquartile range 45-73]; = .02) and presented more often with ≥ 2 comorbidities (40.4% 24.3%; = .02). Compared with nononcological patients, in C19-CP, respiratory failure (29 of 47 321 of 692; = .049) and hospitalization (37 of 47 363 of 692; = .0004) were higher, with comparable frequencies across the waves. Five of 24 and 10 of 27 hospitalized cancer patients in the first and second waves developed SARS-CoV-2 infection during hospitalization.

Conclusion: C19-CP were a vulnerable population, irrespective of the COVID-19 waves. This highlights the need to prioritize vaccinations in oncological patients to safeguard and guarantee optimal anticancer care.
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http://dx.doi.org/10.1200/OP.21.00098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677967PMC
December 2021

Exploring the role of respiratory microbiome in lung cancer: A systematic review.

Crit Rev Oncol Hematol 2021 Aug 29;164:103404. Epub 2021 Jun 29.

Section of Oncology, Department of Medicine, University of Verona and Verona University Hospital Trust, Verona, Italy. Electronic address:

Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients' clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103404DOI Listing
August 2021

Early Progression in Non-Small Cell Lung Cancer (NSCLC) with High PD-L1 Treated with Pembrolizumab in First-Line Setting: A Prognostic Scoring System Based on Clinical Features.

Cancers (Basel) 2021 Jun 11;13(12). Epub 2021 Jun 11.

Division of Thoracic Oncology, European Institute of Oncology IRCCS, 20141 Milano, Italy.

Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored.

Methods: We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model.

Results: Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9-4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0-13, with three-risk group stratification: 0-2 (good prognosis), 3-6 (intermediate prognosis), and 7-13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70-0.81).

Conclusions: We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting.
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http://dx.doi.org/10.3390/cancers13122935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230881PMC
June 2021

[Mutational oncology of lung cancer: molecular markers, drugs, negotiation conditions and experiences in national reference centers.]

Recenti Prog Med 2021 Jun;112(6):419-437

Drugs and Health srl, Roma.

The gradual availability of genomic profiling tests and the "agnostic approvals" from FDA and EMA have opened the oncology mutational model phase, which complements and integrates the traditional hystological approach. The non-small-cell lung cancer (NSCLC) is characterized by many molecular alterations and represents the need of a change from the traditional diagnostic, therapeutic and organisational paradigms to the "mutational" ones. From the Italian National Healthcare System point of view, access and reimbursement of drugs based on the hystological model were managed thorugh the Italian Medicines Agency's (AIFA) monitoring registries and the managed entry agreements: risk-sharing, cost-sharing and payment by results. The Italian reference oncological centres, which contributed to this report with their experiences, have shown the heterogenous approach to the molecular diagnostics (included next generation system tests). Facing the high complexity of the mutational model, outcomes handling and genomic profiling tests access inevitably result different among centres. The activation of multidisciplinary groups for the government of clinical processes, appropriateness and economic sustainability are essential. The Molecular Tumor Board (MTB) allows the management of such complexity, the interpretation of genomic profiling outcomes and the choice of drugs that are alrealdy authorized by AIFA, off-label or still under investigation. Moreover, in order to guarantee the uniformity, the data traceability and the transparency of assessment reports, a network of MTB must be validated by AIFA through specific criteria. To date, the oncological centres presented by this report are undergoing the experimental phase of the national genomic operating system implementation and represent the starting point of the deep organisational changement to the mutational approach and of its real and appropriate integration into the daily clinical practice.
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http://dx.doi.org/10.1701/3620.36025DOI Listing
June 2021

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations.

Cancers (Basel) 2021 May 17;13(10). Epub 2021 May 17.

Thoracic Oncology Unit, Department of Oncology, San Luigi Gonzaga Hospital, University of Torino, 10043 Orbassano, Italy.

Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation-positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co-alterations may predict different outcomes to TKIs.

Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first-line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD-L1 expression was also evaluated.

Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; = 0.088), PFS (mPFS 10.9 vs. 11.2 months; = 0.415) and ORR (55.9% vs. 68.1%; = 0.202) were observed comparing patients without and with co-alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD-L1 expression levels by co-mutational status were found. Significant associations with presence of co-alterations and younger age ( = 0.018) and baseline lymph nodes metastases ( = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, = 0.011).

Conclusions: Pathogenic co-alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.
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http://dx.doi.org/10.3390/cancers13102425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156829PMC
May 2021

Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma.

Cancers (Basel) 2021 May 12;13(10). Epub 2021 May 12.

Department of Oncology, University of Torino, 10043 Orbassano, Italy.

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.

Methods: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation.

Results: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro.

Conclusion: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.
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http://dx.doi.org/10.3390/cancers13102332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151304PMC
May 2021

Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer.

Lung Cancer 2021 07 24;157:9-16. Epub 2021 May 24.

Oncology Department, University of Turin, AOU San Luigi, 10043, Orbassano, Turin, Italy. Electronic address:

Background: The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice.

Methods: UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes.

Results: Data for 104 patients (male: 43 %; median age: 53 [29-80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1-6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1-5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6-12.9) months and median OS was 23.3 (95 % CI: 16.0-NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34).

Conclusions: These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.017DOI Listing
July 2021

Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1-Positive Advanced NSCLC.

J Thorac Oncol 2021 10 26;16(10):1718-1732. Epub 2021 May 26.

The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Introduction: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study.

Methods: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis.

Results: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab.

Conclusions: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.
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http://dx.doi.org/10.1016/j.jtho.2021.05.001DOI Listing
October 2021

Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics.

Eur J Cancer 2021 07 19;151:211-220. Epub 2021 May 19.

Department Pulmonology, Erasmus MC, Rotterdam, the Netherlands.

Background: dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non-small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance.

Patients And Methods: aNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR≤3 = low]. B+C2 dNLR were combined in one score: good = low (B+C2), poor = high (B+C2), intermediate = other situations. In 57 patients, we prospectively explored the immunophenotype of circulating neutrophils, particularly the CD15+CD244-CD16cells (immature) by flow cytometry.

Results: About 1485 patients treatment with ICI were analysed. In ICI-treated patients, high dNLR (B) (~1/3rd) associated with worse progression-free (PFS)/overall survival (OS) (HR 1.56/HR 2.02, P < 0.0001) but not with chemotherapy alone (N = 173). High dNLR at C2 was associated with worse PFS/OS (HR 1.64/HR 2.15, P < 0.0001). When dNLR at both time points were considered together, those with persistently high dNLR (23%) had poor survival (mOS = 5 months (mo)), compared with high dNLR at one time point (22%; mOS = 9.2mo) and persistently low dNLR (55%; mOS = 18.6mo) (P < 0.0001). The dNLR impact remained significant after PD-L1 adjustment. By cytometry, high rate of immature neutrophils (B) (30/57) correlated with poor PFS/OS (P = 0.04; P = 0.0007), with a 12-week death rate of 49%.

Conclusion: The dNLR (B) and its dynamics (C2) under ICI associate with ICI outcomes in aNSCLC. Persistently high dNLR (B+C2) correlated with early ICI failure. Immature neutrophils may be a key subpopulation on ICI resistance.
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http://dx.doi.org/10.1016/j.ejca.2021.03.011DOI Listing
July 2021

Immune-checkpoint inhibition in stage III unresectable NSCLC: Challenges and opportunities in the post-PACIFIC era.

Lung Cancer 2021 07 11;157:85-91. Epub 2021 May 11.

Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy. Electronic address:

The PACIFIC trial marked a new era in the treatment of stage III unresectable NSCLC, establishing durvalumab consolidation as new standard of care worldwide, with about 14 % increase of long-term survival and half of the patients alive at 4 years. A series of intensified immune-checkpoint inhibition regimens are currently under investigation in clinical trials in order to optimize the therapeutic benefit obtained in this population, while the identification of personalized approaches as well as the development of effective treatments in the post-durvalumab progression setting represent an actual and controversial topic for clinical lung cancer research. This review describes the current real-word treatment scenario for stage III unresectable NSCLC in Italy, and provides an updated overview of the upcoming therapeutic strategies under clinical investigation, discussing the most relevant challenges and opportunities featuring the post-PACIFIC era.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.009DOI Listing
July 2021

Black Hairy Tongue After Immune Checkpoint Inhibitors in NSCLC: A Case Report and Review of the Literature.

Clin Lung Cancer 2021 11 26;22(6):e804-e807. Epub 2021 Mar 26.

Department of Oncology at San Luigi Gonzaga University Hospital, University of Torino, Turin, Italy.

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http://dx.doi.org/10.1016/j.cllc.2021.03.008DOI Listing
November 2021
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