Pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: Final analysis of distant metastasis-free survival in the phase 3 KEYNOTE-716 study.

Jason J. Luke UPMC Hillman Cancer Center, Pittsburgh, PA info_outline Jason J. Luke, Paolo Antonio Ascierto, Muhammad Adnan Khattak, Luis de la Cruz Merino, Michele Del Vecchio, Piotr Rutkowski, Francesco Spagnolo, Jacek Mackiewicz, Vanna Chiarion-Sileni, John M. M. Kirkwood, Caroline Robert, Jean-Jacques Grob, Federica de Galitiis, Dirk Schadendorf, Matteo S. Carlino, Larry Wu, Mizuho Fukunaga-Kalabis, Clemens Krepler, Alexander M. Eggermont, Georgina V. Long

Authors Jason J. Luke UPMC Hillman Cancer Center, Pittsburgh, PA info_outline Jason J. Luke, Paolo Antonio Ascierto, Muhammad Adnan Khattak, Luis de la Cruz Merino, Michele Del Vecchio, Piotr Rutkowski, Francesco Spagnolo, Jacek Mackiewicz, Vanna Chiarion-Sileni, John M. M. Kirkwood, Caroline Robert, Jean-Jacques Grob, Federica de Galitiis, Dirk Schadendorf, Matteo S. Carlino, Larry Wu, Mizuho Fukunaga-Kalabis, Clemens Krepler, Alexander M. Eggermont, Georgina V. Long Organizations UPMC Hillman Cancer Center, Pittsburgh, PA, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy, Fiona Stanley Hospital and Edith Cowan University, Perth, Western Australia, Australia, Hospital Universitario Virgen Macarena, Seville, Spain, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Maria Skłodowska-Curie National Institute of Oncology Center, Warsaw, Poland, IRCCS San Martino Polyclinic Hospital, Genoa, Italy, Poznan University of Medical Sciences and Greater Poland Cancer Center, Poznań, Poland, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, Gustave Roussy and Paris-Saclay University, Villejuif, France, AP-HM Hospital, Aix-Marseille University, Marseille, France, Dermopathic Institute of the Immaculate IDI-IRCCS, Rome, Italy, Department of Dermatology, University of Essen, Essen, and German Cancer Consortium, Heidelberg, Germany, Melanoma Institute Australia, The University of Sydney, Westmead and Blacktown Hospitals, Sydney, Australia, Merck & Co., Inc., Rahway, NJ, University Medical Center Utrecht & Princess Máxima Center, Utrecht, Netherlands, Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Background: Adjuvant pembrolizumab significantly improved distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) in patients with resected stage IIB or IIC melanoma versus placebo. We present the protocol-specified final DMFS analysis from KEYNOTE-716 (NCT03553836). Methods: Eligible patients were ≥12 years old with resected stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer, 8th edition, guidelines and a negative sentinel lymph node biopsy. In part 1 of the study, patients were randomly assigned (1:1) to pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for up to 17 cycles (~1 year) or until disease recurrence, unacceptable toxicity, or withdrawal. Randomization was stratified by T category for adults (T3b vs T4a vs T4b), with a separate stratum for pediatric patients. The primary end point was RFS per investigator review. DMFS per investigator review was a secondary end point. The protocol-specified final DMFS analysis was based on a target of 195 DMFS events. No formal hypothesis testing was performed because DMFS and RFS end points were met at previous interim analyses. The data cutoff date for this analysis was January 4, 2023. Results: Overall, 976 patients were randomly assigned to receive pembrolizumab (n = 487) or placebo (n = 489). Median duration of follow-up (time from randomization to the data cutoff date) was 39.4 months (range, 26.0-51.4). Compared with placebo, adjuvant pembrolizumab improved DMFS (medians: not reached; hazard ratio [HR], 0.59 [95% CI, 0.44-0.79]) and RFS (medians: not reached; HR, 0.62 [95% CI, 0.49-0.79]). The 36-month DMFS rate was 84.4% with adjuvant pembrolizumab versus 74.7% with placebo; the 36-month RFS rate was 76.2% with adjuvant pembrolizumab versus 63.4% with placebo. DMFS benefit with adjuvant pembrolizumab over placebo was observed regardless of cancer stage at baseline (stage IIB HR, 0.62 [95% CI, 0.42-0.92]; stage IIC HR, 0.57 [0.36-0.88]). Similar results were observed with RFS (stage IIB HR, 0.58 [95% CI, 0.43-0.79]; stage IIC HR, 0.65 [95% CI, 0.45-0.94]). No new safety signals were observed. Conclusions: With a median follow-up of 39.4 months, adjuvant pembrolizumab for resected stage IIB and IIC melanoma continued to show DMFS and RFS benefit over placebo, with no new safety signals. Clinical trial information: NCT03553836.