Omid Hamid1, Igor Puzanov2, Reinhard Dummer3, Jacob Schachter4, Adil Daud5, Dirk Schadendorf6, Christian Blank7, Lee D Cranmer8, Caroline Robert9, Anna C Pavlick10, Rene Gonzalez11, F Stephen Hodi12, Paolo A Ascierto13, April K S Salama14, Kim A Margolin15, Tara C Gangadhar16, Ziwen Wei17, Scot Ebbinghaus17, Nageatte Ibrahim17, Antoni Ribas18. 1. The Angeles Clinic and Research Institute, Los Angeles, CA, USA. Electronic address: ohamid@theangelesclinic.org. 2. Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. 3. University of Zürich, Zürich, Switzerland. 4. Ella Lemelbaum Institute of Melanoma, Sheba Medical Center, Tel Hashomer, Israel. 5. University of California, San Francisco, San Francisco, CA, USA. 6. University Hospital Essen, Essen, Germany. 7. Netherlands Cancer Institute, Amsterdam, The Netherlands. 8. University of Arizona Cancer Center, Tucson, AZ, USA. 9. Gustave Roussy and Paris-Sud University, Villejuif, France. 10. New York University Cancer Institute, New York, NY, USA. 11. University of Colorado Denver, Aurora, CO, USA. 12. Dana-Farber Cancer Institute, Boston, MA, USA. 13. Istituto Nazionale Tumori Fondazione G. Pascale, Napoli, Italy. 14. Duke Cancer Institute, Durham, NC, USA. 15. City of Hope, Duarte, CA, USA. 16. Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA. 17. Merck & Co., Inc., Kenilworth, NJ, USA. 18. University of California Los Angeles, Los Angeles, CA, USA.
Abstract
AIM: To evaluate the protocol-specified final analysis of overall survival (OS) in the KEYNOTE-002 study (NCT01704287) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory, advanced melanoma. METHODS: In this randomised, phase II study, eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses, previous BRAF or MEK inhibitor or both, if BRAFV600 mutant-positive. Patients were randomised to pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy. Crossover to pembrolizumab was allowed following progression on chemotherapy. The protocol-specified final OS was performed in the intent-to-treat population. Survival was positive if p < 0.01 in one pembrolizumab arm. RESULTS: A total of 180 patients were randomised to pembrolizumab 2 mg/kg, 181 to pembrolizumab 10 mg/kg and 179 to chemotherapy. At a median follow-up of 28 months (range 24.1-35.5), 368 patients died and 98 (55%) crossed over to pembrolizumab. Pembrolizumab 2 mg/kg (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.67-1.10, p = 0.117) and 10 mg/kg (0.74, 0.57-0.96, p = 0.011) resulted in a non-statistically significant improvement in OS versus chemotherapy; median OS was 13.4 (95% CI 11.0-16.4) and 14.7 (95% CI 11.3-19.5), respectively, versus 11.0 months (95% CI 8.9-13.8), with limited improvement after censoring for crossover. Two-year survival rates were 36% and 38%, versus 30%. Progression-free survival, objective response rate and duration of response improved with pembrolizumab versus chemotherapy, regardless of dose. Grade III-V treatment-related adverse events occurred in 24 (13.5%), 30 (16.8%) and 45 (26.3%) patients, respectively. CONCLUSION: Improvement in OS with pembrolizumab was not statistically significant at either dose versus chemotherapy.
RCT Entities:
AIM: To evaluate the protocol-specified final analysis of overall survival (OS) in the KEYNOTE-002 study (NCT01704287) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory, advanced melanoma. METHODS: In this randomised, phase II study, eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses, previous BRAF or MEK inhibitor or both, if BRAFV600 mutant-positive. Patients were randomised to pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy. Crossover to pembrolizumab was allowed following progression on chemotherapy. The protocol-specified final OS was performed in the intent-to-treat population. Survival was positive if p < 0.01 in one pembrolizumab arm. RESULTS: A total of 180 patients were randomised to pembrolizumab 2 mg/kg, 181 to pembrolizumab 10 mg/kg and 179 to chemotherapy. At a median follow-up of 28 months (range 24.1-35.5), 368 patients died and 98 (55%) crossed over to pembrolizumab. Pembrolizumab 2 mg/kg (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.67-1.10, p = 0.117) and 10 mg/kg (0.74, 0.57-0.96, p = 0.011) resulted in a non-statistically significant improvement in OS versus chemotherapy; median OS was 13.4 (95% CI 11.0-16.4) and 14.7 (95% CI 11.3-19.5), respectively, versus 11.0 months (95% CI 8.9-13.8), with limited improvement after censoring for crossover. Two-year survival rates were 36% and 38%, versus 30%. Progression-free survival, objective response rate and duration of response improved with pembrolizumab versus chemotherapy, regardless of dose. Grade III-V treatment-related adverse events occurred in 24 (13.5%), 30 (16.8%) and 45 (26.3%) patients, respectively. CONCLUSION: Improvement in OS with pembrolizumab was not statistically significant at either dose versus chemotherapy.
Authors: Harriet M Kluger; Veronica Chiang; Amit Mahajan; Christopher R Zito; Mario Sznol; Thuy Tran; Sarah A Weiss; Justine V Cohen; James Yu; Upendra Hegde; Elizabeth Perrotti; Gail Anderson; Amanda Ralabate; Yuval Kluger; Wei Wei; Sarah B Goldberg; Lucia B Jilaveanu Journal: J Clin Oncol Date: 2018-11-08 Impact factor: 44.544
Authors: Emmanuel S Antonarakis; Josep M Piulats; Marine Gross-Goupil; Jeffrey Goh; Kristiina Ojamaa; Christopher J Hoimes; Ulka Vaishampayan; Ranaan Berger; Ahmet Sezer; Tuomo Alanko; Ronald de Wit; Chunde Li; Aurelius Omlin; Giuseppe Procopio; Satoshi Fukasawa; Ken-Ichi Tabata; Se Hoon Park; Susan Feyerabend; Charles G Drake; Haiyan Wu; Ping Qiu; Jeri Kim; Christian Poehlein; Johann Sebastian de Bono Journal: J Clin Oncol Date: 2019-11-27 Impact factor: 44.544
Authors: Hayley Standage; Alyssa R Hersh; Aaron Caughey; Matthew Taylor; John Vetto; Dale Han Journal: Ann Surg Oncol Date: 2020-09-19 Impact factor: 5.344
Authors: Igor Puzanov; Antoni Ribas; Caroline Robert; Jacob Schachter; Marta Nyakas; Adil Daud; Ana Arance; Matteo S Carlino; Steven J O'Day; Georgina V Long; Kim A Margolin; Reinhard Dummer; Dirk Schadendorf; Jose Lutzky; Paolo A Ascierto; Ahmad Tarhini; Jianxin Lin; Robin Mogg; Blanca Homet Moreno; Nageatte Ibrahim; Omid Hamid Journal: JAMA Oncol Date: 2020-08-01 Impact factor: 31.777