Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial

Georgina V Long ¹, Jason J Luke ², Muhammad A Khattak ³

¹Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Royal North Shore & Mater Hospitals, Sydney, NSW, Australia.
²Department of Medicine, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
³Fiona Stanley Hospital, Perth, WA, Australia; Edith Cowan University, Perth, WA, Australia.
⁴Medical Oncology Department, Hospital Universitario Virgen Macarena, Seville, Spain.
⁵Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
⁶Department of Soft Tissue, Bone Sarcoma, and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
⁷IRCCS San Martino Polyclinic Hospital, Genoa, Italy.
⁸Department of Medical and Experimental Oncology, Poznan University of Medical Sciences, Poznan, Poland; Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Center, Poznan, Poland.
⁹Istituto Oncologico Veneto, IOV-IRCCS, Padova, Italy.
¹⁰Department of Dermatology, Institut Gustave Roussy, Villejuif, France; Paris-Saclay University, Villejuif, France.
¹¹AP-HM Hospital, Aix-Marseille University, Marseille, France.
¹²Department of Oncology and Dermatological Oncology, Dermopathic Institute of the Immaculate IDI-IRCCS, Rome, Italy.
¹³Department of Dermatology, University Hospital Essen & German Cancer Consortium Partner Site, Essen, Germany.
¹⁴Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Westmead and Blacktown Hospitals, Sydney, NSW, Australia.
¹⁵Elbe Kliniken Buxtehude, Buxtehude, Germany.
¹⁶University Hospital Zürich Skin Cancer Center, Zürich, Switzerland.
¹⁷The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁸Department of Surgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
¹⁹Merck & Co, Rahway, NJ, USA.
²⁰University Medical Center Utrecht & Princess Máxima Center, Utrecht, Netherlands; Comprehensive Cancer Center Munich, Munich, Germany.
²¹Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy.

⁰Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Royal North Shore & Mater Hospitals, Sydney, NSW, Australia.

The Lancet. Oncology +

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October 20, 2022

View abstract on PubMed

Summary

Adjuvant pembrolizumab significantly reduced distant metastasis and recurrence risk in patients with stage IIB or IIC melanoma. This immunotherapy offers a positive benefit-risk profile for resected melanoma patients.

Area Of Science

Oncology
Immunotherapy
Melanoma Research

Background

Stage IIB/IIC melanoma patients face high recurrence risk after surgery.
Adjuvant pembrolizumab demonstrated improved recurrence-free survival in prior analyses.
This study reports on distant metastasis-free survival and longer-term recurrence-free survival.

Purpose Of The Study

To evaluate adjuvant pembrolizumab's efficacy in preventing distant metastasis and recurrence.
To report findings from the third interim analysis of the KEYNOTE-716 trial.
To assess the long-term benefit-risk profile of pembrolizumab in resected melanoma.

Main Methods

Phase 3, double-blind, placebo-controlled trial (KEYNOTE-716) in 160 centers.
976 patients with resected stage IIB/IIC melanoma randomly assigned to pembrolizumab or placebo.
Primary endpoint: recurrence-free survival; secondary endpoint: distant metastasis-free survival.

Main Results

Pembrolizumab significantly improved distant metastasis-free survival (HR 0.64, p=0.0029).
Recurrence risk was lower with pembrolizumab (HR 0.64).
Adverse event profile was consistent with prior pembrolizumab studies; no treatment-related deaths.

Conclusions

Adjuvant pembrolizumab is an effective treatment for resected stage IIB/IIC melanoma.
Significant improvements in distant metastasis-free survival and sustained reduction in recurrence risk observed.
Pembrolizumab maintains a positive benefit-risk profile in the adjuvant setting.