Pembro has well characterized, manageable safety in the advanced setting. Clinical data suggest pembro has a similar profile in the adjuvant setting; further characterization is important given the extended life expectancy of pts with resectable disease.
Safety data from pts with resected stage IIIA-C (AJCC 7th ed) melanoma (KEYNOTE-054), resected stage IB-IIIA (AJCC 7th ed) NSCLC (PEARLS/KEYNOTE-091), RCC post-nephrectomy/metastasectomy (KEYNOTE-564), and resected stage IIB-C (AJCC 8th ed) melanoma (KEYNOTE-716) were pooled. Pts received adjuvant pembro 200 mg (2 mg/kg pediatric pts) Q3W or placebo for up to ∼1 yr. Safety was monitored for ≤30 days after treatment end (90 days for serious AEs). AEs were graded using NCI CTCAE v4.0.
Data from 4125 pts were pooled (pembro, n=2060; placebo, n=2065). Median age was 61.0 yrs; 1351 (65.6%) pts treated with pembro and 1343 (65.0%) with placebo were male. Any-grade treatment-related AEs (TRAEs) occurred in 1620 (78.6%) pts treated with pembro and 1212 (58.7%) with placebo. Grade 3-5 TRAEs occurred in 336 (16.3%) pts treated with pembro and 72 (3.5%) with placebo; most common were diarrhea (n=23; 1.1%), ALT increased (n=20; 1.0%), and colitis (n=20; 1.0%) with pembro and lipase increased (n=13; 0.6%) and fatigue (n=6; 0.3%) with placebo. 4 pts in the pembro group died due to a TRAE. TRAEs led to discontinuation in 326 (15.8%) pts treated with pembro and 44 (2.1%) with placebo. Immune-mediated AEs (imAEs) and infusion reactions occurred in 761 (36.9%) pts treated with pembro and 193 (9.3%) with placebo (grade 3-5: n=181 [8.8%] vs n=23 [1.1%]). Most common imAEs were hypothyroidism (n=382; 18.5%), hyperthyroidism (n=227; 11.0%), and pneumonitis (n=82; 4.0%) with pembro and hypothyroidism (n=76; 3.7%), pneumonitis (n=29; 1.4%), and hyperthyroidism (n=27; 1.3%) with placebo. Median time to onset of first imAE or infusion reaction was 2.6 mo with pembro and 4.1 mo with placebo.
Data from this pooled analysis of >4000 patients across several tumor types show that adjuvant pembro has a manageable safety profile consistent in severity and management with the established profile of pembro in advanced disease.
NCT02362594 (first posted to clinicaltrials.gov: Feb 13, 2015); NCT02504372 (first posted to clinicaltrials.gov: July 21, 2015); NCT03142334 (first posted to clinicaltrials.gov: May 5, 2017); NCT03553836 (first posted to clinicaltrials.gov: Jun 12, 2018).
Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding for this research was provided by Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
J.J. 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M.A. Leiby: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. J. Lin: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. Y. Zhao: Financial Interests, Personal, Full or part-time Employment: Merck; Non-Financial Interests, Personal, Member: Merck. C. Krepler: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Full or part-time Employment: Merck. R.F. Perini: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc. M.C. Pietanza: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A. Samkari: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc. T. Gruber: Financial Interests, Personal, Full or part-time Employment: Merck, Clinical Safety and Risk Management; Financial Interests, Personal, Stocks/Shares: Merck, Clinical Safety and Risk Management; Financial Interests, Institutional, Leadership Role: Merck, Clinical Safety and Risk Management. N. Ibrahim: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A.M.M. Eggermont: Financial Interests, Personal, Speaker’s Bureau: BMS, Merck; Financial Interests, Personal, Advisory Board: Agenus, BioInvent, Brenus,CatalYm, Clover, Ellipses, Galecto, GenOway, GSK, IO Biotech, IQVIA, ISA Pharmaceuticals, Merck/MSD, Sairopa, Scorpion, Sellas, SkylineDX, TigaTX, Trained Therapeutics Discovery; Financial Interests, Personal, Stocks/Shares: IOBiotech, Sairopa, SkylineDX; Financial Interests, Personal, Principal Investigator: KEYNOTE-054; Financial Interests, Personal, Other, IDMC: BioNTech, IQVIA, GSK, Pfizer. All other authors have declared no conflicts of interest.