The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Among patients with resected, stage III cutaneous melanoma in the KEYNOTE-054 trial, patients who crossed over from placebo to pembrolizumab at progression derived more benefit from the drug than patients who were rechallenged with pembrolizumab after progression.1

These results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Alexander Eggermont, MD, PhD, of Princess Máxima Center in Utrecht, Netherlands.

The phase 3 KEYNOTE-054 trial ( Identifier: NCT02362594) included patients with resected, stage III cutaneous melanoma. Initially, 1019 patients were randomly assigned to receive pembrolizumab (200 mg) or placebo every 3 weeks over about 1 year.

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Previous results showed significant improvements in recurrence-free survival and distant metastasis-free survival with pembrolizumab over placebo.2,3

The current analysis focused on overall response rate (ORR), progression-free survival (PFS), and safety in crossover and rechallenge patients.

Patients were eligible for this part of the study if they had disease recurrence, without brain metastasis, and a performance status of 0-2. Patients who were rechallenged had to have relapsed more than 6 months after they completed their initial treatment with pembrolizumab.

Of the 175 patients included, 155 had crossed over from placebo and 20 were rechallenged with pembrolizumab. All of these patients received pembrolizumab (200 mg) every 3 weeks for a maximum of 2 years.

There were 23 patients in the crossover group and 1 in the rechallenge group who completed treatment as planned. Ten patients in the crossover group and 5 in the rechallenge group were still on treatment at last follow-up.

Reasons for early treatment discontinuation included progression (76 crossover, 11 rechallenge), toxicity (19 crossover, 1 rechallenge), patient or investigator decision (19 crossover, 2 rechallenge), loss to follow-up (1 crossover), recurrence and new malignancy (1 crossover), or other reasons (6 crossover).

The ORR was 38.8% in the crossover group and 11.1% in the rechallenge group. There were 14 complete responses in the crossover group and 1 complete response in the rechallenge group.

The median PFS was longer in the crossover group than in the rechallenge group — 8.5 months and 4.1 months, respectively. The 3-year PFS was 32% in the crossover group, and the 1-year PFS was 40% in the rechallenge group.

The incidence of grade 1-4 immune-related adverse events was 30.3% in crossover patients and 20.0% in rechallenged patients.

Dr Eggermont noted that PFS and ORR results in crossover patients were similar to PFS and ORR outcomes of patients treated with pembrolizumab in the KEYNOTE-006 trial4 and patients treated with nivolumab in the CHECKMATE-067 trial5.

Disclosures: This research was supported by Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


  1. Eggermont AM, Meshcheryakov A, Atkinson V, et al. Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma. J Clin Oncol. 2021;39:(suppl 15; abstr 9500). doi:10.1200/JCO.2021.39.15_suppl.9500
  2. Eggermont AM, Blank CU, Mandalà M, et al. Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up. J Clin Oncol. 2020; 38:(suppl 15; abstr 1000). doi:10.1200/JCO.2020.38.15_
  3. Eggermont AM, Blank CU, Mandalà M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(5):643-654. doi: 10.1016/S1470-2045(21)00065-6
  4. Robert C, Ribas A, Schachter  J, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019;20(9):1239-1251. doi:10.1016/S1470-2045(19)30388-2.
  5. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017;377:1345-1356. doi:10.1056/NEJMoa1709684