Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma

Sapna P. Patel, Megan Othus, Yuanbin Chen, G. Paul Wright, Kathleen J. Yost, John R. Hyngstrom, Siwen Hu-Lieskovan, Christopher D. Lao, Leslie A. Fecher, Thach Giao Truong, Jennifer L. Eisenstein, Sunandana Chandra, Jeffrey A. Sosman, Kari L. Kendra, Richard C. Wu, Craig E. Devoe, Gary B. Deutsch, Aparna Hegde, Maya Khalil, Ankit ManglaAmy M. Reese, Merrick I. Ross, Andrew S. Poklepovic, Giao Q. Phan, Adedayo A. Onitilo, Demet G. Yasar, Benjamin C. Powers, Gary C. Doolittle, Gino K. In, Niels Kokot, Geoffrey T. Gibney, Michael B. Atkins, Montaser Shaheen, James A. Warneke, Alexandra Ikeguchi, Jose E. Najera, Bartosz Chmielowski, Joseph G. Crompton, Justin D. Floyd, Eddy Hsueh, Kim A. Margolin, Warren A. Chow, Kenneth F. Grossmann, Eliana Dietrich, Victor G. Prieto, Michael C. Lowe, Elizabeth I. Buchbinder, John M. Kirkwood, Larissa Korde, James Moon, Elad Sharon, Vernon K. Sondak, Antoni Ribas

Research output: Contribution to journalArticlepeer-review

229 Scopus citations

Abstract

Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. Methods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. Results: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P=0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. Conclusions: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified.

Original languageEnglish (US)
Pages (from-to)813-823
Number of pages11
JournalNew England Journal of Medicine
Volume388
Issue number9
DOIs
StatePublished - 2023
Externally publishedYes

Keywords

  • Dermatology
  • Hematology/Oncology
  • Skin Cancer
  • Surgery
  • Surgery General
  • Treatments in Oncology

ASJC Scopus subject areas

  • General Medicine

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