Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non–Small-Cell Lung Cancer: AVAPERL (MO22089)

Authors

Fabrice Barlesi

Fabrice Barlesi, Aix Marseille University–Assistance Publique Hôpitaux de Marseille and Centre d'Investigation Clinique, Marseille; Arnaud Scherpereel, Hôpital Calmette, Centre Hospitalier Régional Universitaire de Lille, Lille, France; Achim Rittmeyer, Lungenfachklinik Immenhausen, Immenhausen, Germany; Antonio Pazzola, Ospedale Civile Santissima, Annunziata, Sassari, Italy; Neus Ferrer Tur, Hospital Son Llàtzer, Palma de Majorca, Spain; Joo-Hang Kim, Yonsei University College of Medicine; Myung-Ju Ahn, Sungkyunkwan University School of Medicine, Seoul, South Korea; Joachim G.J.V. Aerts, Amphia Hospital, Breda, and Erasmus Medical Center, Rotterdam; Harry J.M. Groen, University Medical Center Groningen, Groningen, the Netherlands; Vera Gorbunova, N.N. Blokhin Cancer Research Centre of Russia, Moscow, Russia; Anders Vikström, Lungkliniken, Linköping, Sweden; and Elaine K. Wong, Pablo Perez-Moreno, and Lada Mitchell, F. Hoffmann-La Roche, Basel, Switzerland.

Fabrice Barlesi, Arnaud Scherpereel, Achim Rittmeyer, Antonio Pazzola, Neus Ferrer Tur, Joo-Hang Kim, Myung-Ju Ahn, Joachim G.J.V. Aerts, Vera Gorbunova, Anders Vikström, Elaine K. Wong, Pablo Perez-Moreno, Lada Mitchell, Harry J.M. Groen

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Purpose

Maintenance therapy is associated with improved survival in patients with non–small-cell lung cancer (NSCLC), but few studies have compared active agents in this setting. AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment.

Patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m², and pemetrexed 500 mg/m² once every 3 weeks for four cycles. Those achieving response or stable disease were randomly assigned at a ratio of 1:1 to maintenance bevacizumab 7.5 mg/kg or bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m² once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) after random assignment.

In total, 376 patients received induction treatment, 71.9% achieved disease control, and 67.3% were randomly assigned to maintenance therapy, with 125 and 128 receiving single-agent bevacizumab and bevacizumab plus pemetrexed treatment, respectively. At a median follow-up of 8.1 months, PFS from random assignment was significantly improved in the bevacizumab plus pemetrexed arm (median, 3.7 v 7.4 months; hazard ratio, 0.48; 95% CI, 0.35 to 0.66; P < .001) per a stratified model. The PFS benefit extended across age, performance status, smoking history, and induction response (stable disease v partial response) subgroups. Any grade, grade ≥ 3, and serious adverse events occurred more often with bevacizumab plus pemetrexed maintenance. No new safety signals were observed.

In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.