Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Progression after the next line of therapy (PFS2) and updated OS among patients with advanced NSCLC and PD-L1 tumor proportion score (TPS) ≥50% enrolled in KEYNOTE-024. (#44)

Julie R. Brahmer 1 , Delvys Rodríguez-Abreu 2 , Andrew G. Robinson 3 , Rina Hui 4 , Tibor Csőszi 5 , Andrea Fülöp 6 , Maya Gottfried 7 , Nir Peled 8 , Ali Tafreshi 9 , Sinead Cuffe 10 , Mary O’Brien 11 , Suman Rao 12 , Katsuyuki Hotta 13 , Melanie A. Leiby 14 , Jessica McLean 14 , Yue Shentu 14 , Reshma Rangwala 14 , Martin Reck 15
  1. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
  2. Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain
  3. Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada
  4. Westmead Hospital and the University of Sydney, Sydney, NSW, Australia
  5. Jász-Nagykun-Szolnok County Hospital, Szolnok, Hungary
  6. Országos Korányi TBC és Pulmonológiai Intézet, Budapest, Hungary
  7. Meir Medical Center, Kfar-Saba, Israel
  8. Davidoff Cancer Center, Tel Aviv University, Petah Tikva, Israel
  9. Southern Medical Day Care Centre, Wollongong, NSW, Australia
  10. St. James’s Hospital and Cancer Trials Ireland (formerly ICORG – All Ireland Cooperative Oncology Research Group), Dublin, Ireland
  11. The Royal Marsden Hospital, Sutton, Surrey, United Kingdon
  12. MedStar Franklin Square Hospital, Baltimore, MD, USA
  13. Okayama University Hospital, Okayama, Japan
  14. Merck & Co., Inc., Kenilworth, NJ, USA
  15. Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf, Germany


In KEYNOTE-024 (NCT02142738), pembrolizumab was superior to chemotherapy as 1L therapy for advanced NSCLC with PD-L1 TPS ≥50% and no sensitizing EGFR mutations/ALK translocations. After median follow-up of 11.2 mo, HR was 0.50 for PFS by independent central radiologic review (P<0.001) and 0.60 for OS (P=0.005). We present PFS2 and updated OS.


305 patients were randomized to pembrolizumab 200 mg Q3W (n=154) or investigator-choice platinum-doublet chemotherapy with optional pemetrexed maintenance for nonsquamous histology (n=151). Patients in the chemotherapy arm could cross over to pembrolizumab upon PD (2L+). Kaplan-Meier PFS2 and OS were calculated in all allocated patients. PFS2 was defined as time from randomization to investigator-determined PD after start of 2L therapy, discontinuation of 2L therapy, or death, whichever occurred first; patients alive and without 2L PD were censored at last known survival. There was no adjustment for multiplicity.


As of Jan 5, 2017, 48 patients in the pembrolizumab arm and 97 in the chemotherapy arm had received 2L+ therapy, including 79 who crossed over from chemotherapy to pembrolizumab per protocol. 46 (30%) patients continued on 1L pembrolizumab therapy or in follow-up. Median (95% CI) PFS2 was 18.3 mo (12.7-NE) for patients initially assigned to 1L pembrolizumab and 8.4 mo (6.8-9.8) for those assigned to 1L chemotherapy (HR, 0.54; 95% CI, 0.40-0.72; nominal P<0.001). There were 63 deaths in the pembrolizumab arm and 84 in the chemotherapy arm. Median (95% CI) OS was longer for 1L pembrolizumab (not reached, [19.4 mo-NE]) vs 1L chemotherapy (14.5 mo [9.8-19.6]; HR, 0.63; 95%CI, 0.46-0.88; nominal P=0.003).


Fewer pembrolizumab patients received 2L+ therapy because of the significant improvement in PFS observed for pembrolizumab in the 1L setting. Median PFS2 was substantially improved for pembrolizumab vs chemotherapy. Updated OS maintained consistent superiority of 1L pembrolizumab, despite increased crossover from 1L chemotherapy.