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

• Published in: European journal of cancer (1990) 2024-08, Vol.207, p.114146, Article 114146
• Main Authors: Luke, Jason J., Long, Georgina V., Robert, Caroline, Carlino, Matteo S., Choueiri, Toni K., Haas, Naomi B., O’Brien, Mary, Paz-Ares, Luis, Peters, Solange, Powles, Thomas, Leiby, Melanie A., Lin, Jianxin, Zhao, Yujie, Krepler, Clemens, Perini, Rodolfo F., Catherine Pietanza, M., Samkari, Ayman, Gruber, Todd, Ibrahim, Nageatte, Eggermont, Alexander M.M.
• Format: Article
• Language: English
• Subjects: 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, non–small cell lung; Carcinoma, renal cell; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Chemotherapy, Adjuvant; Clinical Trial, Phase III; Clinical Trials, Phase III as Topic; Female; Humans; Immune checkpoint inhibitors; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Pooled analysis; Programmed cell death 1 receptor; Young Adult
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114146

The safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials. 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. 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. Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease. •Data were pooled from 4125 patients treated with adjuvant pembrolizumab or placebo.•Treatment-related AEs occurred in 78.6 % with pembrolizumab (grade 3–5, 16.3 %).•Immune-mediated AEs occurred in 36.2 % with pembrolizumab (grade 3–5, 8.6 %).•Corticosteroids for immune-mediated AEs were required for 35.2 % with pembrolizumab.•Adjuvant pembrolizumab had a safety profile comparable to that of advanced disease.