Shirish Gadgeel1, Delvys Rodríguez-Abreu2, Giovanna Speranza3, Emilio Esteban4, Enriqueta Felip5, Manuel Dómine6, Rina Hui7, Maximilian J Hochmair8, Philip Clingan9, Steven F Powell10, Susanna Yee-Shan Cheng11, Helge G Bischoff12, Nir Peled13, Francesco Grossi14, Ross R Jennens15, Martin Reck16, Edward B Garon17, Silvia Novello18, Belén Rubio-Viqueira19, Michael Boyer20, Takayasu Kurata21, Jhanelle E Gray22, Jing Yang23, Tuba Bas23, M Catherine Pietanza23, Marina C Garassino24. 1. Karmanos Cancer Institute, Detroit, MI. 2. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 3. Centre Integré de Cancérologie de la Montérégie, Hôpital Charles-Le Moyne, Greenfield Park, Quebec, Canada. 4. Hospital Universitario Central de Asturias, Oviedo, Spain. 5. Vall d'Hebron University, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 6. Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain. 7. Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia. 8. Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna, Austria. 9. Southern Medical Day Care Centre, Wollongong, New South Wales, Australia. 10. Sanford Health, Sioux Falls, SD. 11. Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 12. Thoraxklinik, Heidelberg, Germany. 13. Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel. 14. Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. 15. Epworth Healthcare, Richmond, Victoria, Australia. 16. LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. 17. David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA. 18. Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria San Luigi, Orbassano, Italy. 19. Hospital Universitario Quirónsalud Madrid, Madrid, Spain. 20. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 21. Kansai Medical University Hospital, Osaka, Japan. 22. Moffitt Cancer Center, Tampa, FL. 23. Merck & Co, Kenilworth, NJ. 24. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
PURPOSE: In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680). METHODS: Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in theplacebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. RESULTS: As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. CONCLUSION: First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.
RCT Entities:
PURPOSE: In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumorprogrammed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680). METHODS:Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. RESULTS: As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. CONCLUSION: First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.
Authors: Timothy A Yap; Eileen E Parkes; Weiyi Peng; Justin T Moyers; Michael A Curran; Hussein A Tawbi Journal: Cancer Discov Date: 2021-04-02 Impact factor: 39.397
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675
Authors: Michael Zhang; Adrian J Rodrigues; Erqi L Pollom; Iris C Gibbs; Scott G Soltys; Steven L Hancock; Joel W Neal; Sukhmani K Padda; Kavitha J Ramchandran; Heather A Wakelee; Steven D Chang; Michael Lim; Melanie Hayden Gephart; Gordon Li Journal: J Neurooncol Date: 2021-01-07 Impact factor: 4.130