J Clin Oncol 2017 Jun 14;35(16):1786-1794. Epub 2017 Mar 14.
Marc P.E. André, Université Catholique de Louvain, Yvoir; Catherine Fortpied, Valeria Fiaccadori, and Tiana Raveloarivahy, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Théodore Girinsky and Christophe Fermé, Institut Gustave Roussy, Villejuif; Oumédaly Reman, Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire, Caen; Pauline Brice, Assistance Publique des Hopitaux de Paris Hôpital Saint-Louis; Richard Delarue, Assistance Publique des Hopitaux de Paris Hôpital Universitaire Necker-Enfants Maladies, Paris; Olivier Casasnovas, Centre Hospitalier Universitaire le Bocage and Institut National de la Santé et de la Recherche Médicale, Dijon; Véronique Edeline, Hôpital René Hugenin-Institut Curie, Saint Cloud; Réda Bouabdallah, Institut Paoli Calmette, Marseille; Catherine Sebban, Hematology Centre Léon Bérard, Lyon; Aspasia Stamatoullas, Centre Henri Becquerel, Rouen; Michel Meignan, Henri Mondor University Hospitals, Créteil, France; Massimo Federico and Monica Bellei, University of Modena and Reggio Emilia, Modena; Manuel Gotti, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia; Alessandro Re, Spedali Civili Hospital, Brescia; Francesco Merli and Annibale Versari, Arcispedale Santa Maria Nuova Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy; Richard van der Maazen and John Raemaekers, Radboud University Medical Center, Nijmegen; Gustaaf van Imhoff, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands; and Lena Specht and Martin Hutchings, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated-according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)-stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET-361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.