NEW YORK — Nivolumab and pembrolizumab exhibited different toxicity profiles and appeared associated with different adverse event frequencies when used as monotherapy for melanoma, according to study results presented at HemOnc Today Melanoma and Cutaneous Malignancies.
An analysis of FDA–approved dosing revealed higher rates of diarrhea, nausea and vomiting among nivolumab-treated patients, and higher rates of myalgia and cough in pembrolizumab-treated patients.
Melinda B. Chu, MD, of OncoDerm Associates in St. Louis and the department of dermatology at Saint Louis University, and colleagues hypothesized that the anti–PD-1 antibodies nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck) would exhibit different toxicity profiles even though they have comparable chemical structures and have been associated with similar response rates.
Melinda B. Chu
Chu and colleagues searched PubMed to assess types and frequencies of adverse events associated with the two agents.
The researchers analyzed data for FDA–approved dosing for both agents: 3 mg/kg every 2 weeks for nivolumab, and 2 mg/kg every 3 weeks for pembrolizumab. Investigators also evaluated pembrolizumab at two other doses: 10 mg/kg every 2 weeks and 10 mg/kg every 3 weeks.
The analysis restricted to FDA–approved dosing included 915 nivolumab-treated patients and 289 pembrolizumab-treated patients. The analysis of all dosing levels included 915 nivolumab-treated patients and 1,394 pembrolizumab-treated patients.
Researchers recorded adverse events that occurred at frequencies of at least 1% for both drugs (all doses, n = 26; FDA-approved doses, n = 24).
In the analysis of all dosing levels, differences in proportion of 11 of the 26 identified adverse events reached statistical significance: diarrhea (16.1% for nivolumab vs. 11.8% for pembrolizumab; P = .0031), nausea (12% vs. 8.9%; P = .0149), vomiting (4.8% vs. 2.8%; P = .0111), asthenia (2.3% vs. 8%; P < .002), fatigue (29.4% vs. 19.2%; P < .0002), increased aminotransferase (2.7% vs. 5.4%; P = .0022), decreased appetite (7% vs. 3.4%; P < .0002), arthralgia (6.9% vs. 10.3%; P = .0054), myalgia (1% vs. 5.7%; P < .0002), cough (1.1% vs. 4%; P < .0002)and rash (10.5% vs. 15.6%; P = .0004).
In the analysis restricted to FDA-approved dosing, the difference reached statistical significance for five adverse events: diarrhea (16.1% for nivolumab vs. 5.5% for pembrolizumab; P < .0002), nausea (12% vs. 5.9%; P = .0031), vomiting (4.8% vs. 1.7%; P = .0209), myalgia (1% vs. 4.5%; P < .0002) and cough (1.1% vs. 3.5%; P = .0061).
“The recognition of the differences between nivolumab and pembrolizumab may help clinicians tailor melanoma treatment to each patient,” Chu and colleagues concluded. – by Mark Leiser
Chu MB, et al. Comparison of adverse effects of nivolumab and pembrolizumab monotherapy in melanoma. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; March 24-25, 2017; New York.
Disclosure: Chu reports no relevant financial disclosures. One other researcher reports grants from Merck for an investigator-initiated trial of neoadjuvant pembrolizumab for unresectable melanoma.