Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC).

Author:

Choueiri Toni K.1,Tomczak Piotr2,Park Se Hoon3,Venugopal Balaji4,Ferguson Thomas5,Symeonides Stefan N.6,Hajek Jaroslav7,Chang Yen-Hwa8,Lee Jae-Lyun9,Sarwar Naveed10,Gurney Howard11,Gross-Goupil Marine12,Mahave Mauricio13,Haas Naomi B.14,Sawrycki Piotr15,Zhang Tian16,Cornell Jerry17,Elfiky Aymen17,Burgents Joseph E.17,Powles Thomas18

Affiliation:

1. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

2. Poznan University of Medical Sciences, Poznan, Poland

3. Sungkyunkwan University, Samsung Medical Center, Seoul, Korea, Republic of (South)

4. Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, United Kingdom

5. Fiona Stanley Hospital, Perth, Western Australia, Australia

6. Edinburgh Cancer Centre and University of Edinburgh, Edinburgh, United Kingdom

7. Fakultni Nemocnice Ostrava, Ostrava, Czech Republic

8. Taipei Veterans General Hospital, Taipei, Taiwan

9. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

10. Imperial College Healthcare NHS Trust, London, United Kingdom

11. Macquarie University Hospital, Sydney, NSW, Australia

12. Centre Hospitalier Universitaire de Bordeaux - Hôpital Saint-André, Bordeaux, France

13. Fundacion Arturo Lopez Perez FALP, Santiago, Chile

14. Abramson Cancer Center, Penn Medicine, Philadelphia, PA

15. Provincial Hospital in Torun, Torun, Poland

16. University of Texas Southwestern Medical Center, Dallas, TX

17. Merck & Co., Inc., Rahway, NJ

18. Barts Health NHS Trust and the Royal Free NHS Foundation Trust, Barts Cancer Institute, and Queen Mary University of London, London, United Kingdom

Abstract

LBA359 Background: The randomized, multicenter, double-blind, phase 3 KEYNOTE-564 study (NCT03142334) showed that adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo following nephrectomy in participants (pts) with ccRCC at an increased risk of recurrence. We report results from the third prespecified interim analysis with a median follow-up of ~57 months. Methods: Pts were aged ≥18 years and had histologically confirmed ccRCC with or without sarcomatoid features, increased risk of recurrence, ECOG PS of 0 or 1, nephrectomy and/or metastasectomy ≤12 weeks before randomization, and no prior systemic therapy for RCC. Pts were randomly allocated 1:1 to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≥17 cycles (~1 year) or until disease recurrence, intolerable toxicity, or withdrawal of consent. DFS by investigator assessment was the primary end point. Overall survival (OS) was a key secondary end point. Safety was a secondary end point. Results: 994 pts were randomized 1:1 to pembrolizumab (n=496) or placebo (n=498). The median time from randomization to data cut-off date of September 15, 2023, was 57.2 months (range, 47.9−74.5). Statistically significant improvement in OS was observed with pembrolizumab vs placebo (medians not reached, HR 0.62, 95% CI 0.44−0.87; P=.0024). A total of 55 OS events were observed in the pembrolizumab arm and 86 in the placebo arm. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86.0% with placebo. OS benefit was observed across key subgroups, including in pts with M0 disease (HR 0.63, 95% CI 0.44−0.90) or M1 NED (HR 0.51, 95% CI 0.15−1.75), with PD-L1 CPS <1 (HR 0.65, 95% CI 0.31−1.38) or CPS ≥1 (HR 0.62, 95% CI 0.42−0.91), and with presence (HR 0.69, 95% CI 0.28−1.70) or absence (HR 0.57, 95% CI 0.39−0.84) of sarcomatoid features. The observed DFS benefit with pembrolizumab vs placebo was consistent with prior interim analyses (HR 0.72; 95% CI 0.59−0.87). No new safety signals were observed. Conclusions: After a median of ~57 months of follow-up, adjuvant pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in overall survival versus placebo in participants with RCC at increased risk of recurrence post surgery. KEYNOTE-564 is the first phase 3 study to show improved survival with any adjuvant therapy in RCC. These results continue to support adjuvant pembrolizumab as a standard of care. Clinical trial information: NCT03142334 .

Funder

Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

Publisher

American Society of Clinical Oncology (ASCO)

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