Safety of pembrolizumab as adjuvant therapy in a pooled analysis of phase 3 clinical trials of melanoma, non-small cell lung cancer, and renal cell carcinoma

Eur J Cancer. 2024 Aug:207:114146. doi: 10.1016/j.ejca.2024.114146. Epub 2024 May 31.

Abstract

Background: The safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials.

Methods: Patients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non-small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment.

Results: Data were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0-18.9) with pembrolizumab and 11.2 months (0.0-18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3-5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3-5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3-5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3-5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively.

Conclusions: Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease.

Keywords: Carcinoma, non–small cell lung; Carcinoma, renal cell; Clinical Trial, Phase III; Immune checkpoint inhibitors; Melanoma; Pooled analysis; Programmed cell death 1 receptor.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents, Immunological* / adverse effects
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / pathology
  • Chemotherapy, Adjuvant
  • Clinical Trials, Phase III as Topic*
  • Female
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / pathology
  • Middle Aged
  • Young Adult

Substances

  • pembrolizumab
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological