Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial
Open accessAbstract
Background The randomized, phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer (nsNSCLC). Progression-free survival (PFS) was significantly prolonged with bevacizumab-pemetrexed, but overall survival (OS) data were immature. In this article, we report an independent, updated analysis of survival outcomes in AVAPERL.Patients and methods Patients with advanced nsNSCLC received first-line bevacizumab (7.5 mg/kg), cisplatin (75 mg/m(2)), and pemetrexed (500 mg/m(2)) every 3 weeks (q3w) for four cycles. Nonprogressing patients were randomized to maintenance bevacizumab (7.5 mg/kg) or bevacizumab-pemetrexed (500 mg/m(2)) q3w until progression or consent withdrawal. The primary end point of the trial was PFS; in this independent OS analysis, participating study centers were contacted to collect survival data on patients still alive at the time of the first analysis.Results A total of 376 patients received induction treatment. Disease control was confirmed in 71.9% of patients; 253 patients were randomized to maintenance treatment with bevacizumab (n = 125) or bevacizumab-pemetrexed (n = 128). At a median follow-up of 14.8 months, patients allocated to bevacizumab-pemetrexed had significantly improved PFS versus those on bevacizumab when measured from randomization [7.4 versus 3.7 months, hazard ratio (HR), 0.57, 95% confidence interval (CI) 0.44-0.75); P < 0.0001]. OS events occurred in 58% of all patients. OS was numerically longer with bevacizumab-pemetrexed versus bevacizumab when measured from randomization [17.1 versus 13.2 months, HR 0.87 (0.63-1.21); P = 0.29]. Second-line therapy was administered in 77% and 70% of patients in the bevacizumab and bevacizumab-pemetrexed arms, respectively. No new adverse events were reported during this updated analysis.Conclusion In an unselected population of nsNSCLC patients achieving disease control on platinum-based induction therapy, maintenance with bevacizumab-pemetrexed was associated with a nonsignificant increase in OS over bevacizumab alone.
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A trend towards improved OS was seen when analysing 58% of events among 253 randomised patients in that study.
“although a trend towards improved OS was seen when analysing 58% of events of 253 patients randomised for this study [83].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [83]
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- We acknowledge Maria Luz Amador, Beatrix Lutiger, and Stefanie Srock, (F. Hoffmann-La Roche Ltd.) for their critical input on this manuscript. In addition, we thank Andrea Schulze (Parexel International, Berlin) for her contributions to the statis- tical analysis, and we acknowledge the contributions of the AVAPERL study investigators. France: Eric Pichon (Hôpital Bretonneau, Tours), Denis Moro-Sibilot (Hôpital Albert Michallon, Grenoble [La Tronche]), Lidia Petit (Hôpital Robert Debre, Reims), Michael Hummelsberger (Centre De Radiothérapie Onco Médicale, Beziers), Gael Deplanque, (Gh Paris Saint Joseph, Paris), Maurice Perol (Hôpital De La Croix Rousse, Lyon), Roland Schott (Centre Paul Strauss, Strassbourg), Radj Gervais (Centre Françoise Baclesse, Caen), Pierre-Jean Souquet (Centre Hospitalier Lyon-Sud, Pierre Bénite), Francoise Guichard (Polyclinique Bordeaux Nord Aquitaine, Bordeaux), Pierre Fournel (Hôpital Nord, Saint-Etienne), Pascal Thomas (CHI des Alpes du Sud Site de Gap, Gap), Jean Domas (Hôpital Saint Jean, Perpignan), Henri Janicot (Hôpital Gabriel Montpied, Clermont-Ferrand), Dominique Genet (Clinique Chenieux, Limoges), Gerard Zalcman (Hôpital Cote De Nacre, Caen), Henri Berard (HIA Sainte Anne, Toulon), Isabelle Monnet (Centre Hospitalier Intercommunal, Creteil), Bénédicte Etiene- Mastroianni (Hôpital Louis Pradel, Bron), Lionel Falchero (Hôpital Nord Ouest, Gleize), Bernard Milleron (Hôpital Tenon, Paris), Christos Chouaid (Hôpital Saint Antoine, Paris); Germany: Frank Griesinger (Pius-Hospital, Oldenburg), Hubert Wirtz (Universitätsklinikum Leipzig, Leipzig), Yon-dschun Ko (Johanniter-Krankenhaus, Bonn), Corinna Eschbach (Asklepios Klinik Harburg, Hamburg), Elke Jaeger (Nordwest Klinik F., Frankfurt), Claus Steppert (Bezirksklinikum Obermain, Ebensfeld), Martin Reck (Krankenhaus Grosshansdorf, Grosshansdorf), Rudolf Huber (Ludwig-Maximilians Uni Klinik Innenstadt, Leipzig), Parvis Sadjadian (Johannes Wesling Klinikum Minden, Minden), Christian Grohé (Evang. Lungenklinik Berlin, Berlin), Bernhard Heinrich (Haematologisch-Onkologische Praxis; Dr Med Brudler, Heinrich, Bangerter, Muenchen), Joerg Mezger (St Vincentius Ziekenhuis, Nieuwegein), B.E.E.M. Van den Borne (Catharina Ziekenhuis, Eindhoven), J.C.C.M. in 't Veen (Sint Franciscus Gasthuis, Rotterdam), J.A. Burgers (Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam), F.P.J. Peters (Orbis Medisch Centrum, Sittard), Marten De Vries (Zaans Medisch Centrum, Zaandam); Russian Federation: Sergey Orlov (Research Institute of Pulmo- nology, St Petersburg), Rimma Savkova (Moscow Regional Oncology Hospital, Balashikha), Viktoriay Dvornichenko (Regi- onal Oncology Hospital, Irkutsk), Igor Polyakov (Clinical Regional Hospital #4, Krasnodar); Spain: Pilar Garrido Lopez (Hospital Ramon Y Cajal, Madrid), Juana Oramas (Hospital Univ.
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- Authors
- Barlesi, F., Scherpereel, A., Gorbunova, V., Gervais, R., Vikström, A., Chouaid, C., Chella, A., Kim, J. H., Ahn, M. J., Reck, M., Pazzola, A., Kim, H. T., Aerts, J. G., Morando, C., Loundou, A., Groen, H. J. M., & Rittmeyer, A.
- Affiliations
- Centre Hospitalier Universitaire de Lille (FR)
- Centre François Baclesse (FR)
- Linköping University Hospital (SE)
- Assistance Publique – Hôpitaux de Paris (FR)
- University of Pisa (IT)
- Yonsei University (KR)
- Samsung Medical Center (KR)
- LungenClinic Grosshansdorf (DE)
- National Cancer Center (KR)
- Erasmus MC (NL)
- Assistance Publique Hôpitaux de Marseille (FR)
- University Medical Center Groningen (NL)
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 25
- Issue
- 5
- Pages
- 1044-1052
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2128002599
- Cited by
- 165
- References
- 23
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 10 · 2020: 17 · 2019: 21 · 2018: 19 · 2017: 18 · 2016: 25 · 2015: 22 · 2014: 9
- FWCI
- 19.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- F. Hoffmann-La Roche, Ltd (NCT00961415)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- bevacizumab, pemetrexed, maintenance therapy, cisplatin, first-line chemotherapy, overall survival, progression-free survival, anti-VEGF therapy, second-line therapy, EGFR tyrosine kinase inhibitors, EGFR mutation status, predictive biomarkers, quality of life, patient-reported outcomes
- MeSH terms
- Bevacizumab, Pemetrexed, Adenocarcinoma, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Cisplatin, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Quality of Life, Proportional Hazards Models, Treatment Outcome, Disease-Free Survival, Kaplan-Meier Estimate, Maintenance Chemotherapy, Antibodies, Monoclonal, Humanized
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