Detailed safety profile of the anti-PD-1 monoclonal antibody pembrolizumab in 78 consecutive patients (pts) with advanced melanoma

Background

The programmed death receptor 1 (PD-1) inhibitor pembrolizumab has shown clinical benefit with acceptable tolerability in pts with advanced melanoma. We provide detailed information on the safety profile of pembrolizumab in one institution.

Methods

In the KEYNOTE-001 phase 1 trial, pts with advanced melanoma received either pembrolizumab 10 mg/kg every 2 weeks or 10 mg/kg every 3 weeks or 2 mg/kg every 3 weeks until disease progression or severe toxicity. The severity of the adverse events (AEs) was graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 4.0. AEs were depicted using percentages. The cumulative incidence of AEs from treatment initiation was estimated with the Kaplan-Meier method.

Results

78 pts received pembrolizumab: 2 mg/kg Q3W (n = 20), 10 mg/kg Q2W (n = 23) or 10 mg/kg Q3W (n = 35) in our institution. The median duration of follow-up was 20 months. Treatment was well tolerated, with a similar cumulative incidence of AEs with the 3 pembrolizumab dosing regimens and no drug-related death. AEs of any grade were observed in 73 pts (94%). The most common AEs were fatigue, arthralgia, vitiligo, pruritus and diarrhea. The time to onset of AEs did not differ between the 3 dosing regimens (p > 0.4). The median times to onset of skin disorders and musculoskeletal disorders were 8.3 months and 17.3 months respectively, whereas the median time to onset of gastrointestinal disorders was not reached. Grade 3 or 4 AEs occurred in 11 pts (14%). Permanent discontinuation was reported in 7 pts (9%) due to treatment-related AEs, including colitis, thromboembolic events, pneumonitis, interstitial nephritis and hemolytic anemia. Unexpected AEs were reported, including infections in 31 pts (40%), teeth/gingival abnormalities in 8 pts (10%) and pleural effusion in 3 (4%). Vitiligo was reported in 21 pts (27%) and seemed associated with clinical response.

Conclusions

This safety analysis provides a detailed characterization of the AE profile of pembrolizumab, and reports new unanticipated AEs potentially related to the drug.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

E. Routier: Consultant of and BMS and Roche. C. Mateus: Consultant of BMS and Merck. F. Carbonnel: Consultant of Abbvie, Enterome, Ferring, Genentech, Hospira, Jansen, Mayoly, MSD, Otsuka, Splindler, and Takeda and Vifor. O. Lambotte: Consultant of Genzyme and MSD. J-C. Soria: Consultant of Astra-Zeneca, Merus, MSD, Pfizer, Roche, Servier and Symphogen. A. Eggermont: Member of the scientific advisory board of BMS, Incyte, Medimmune and Merck. C. Robert: Consultant of Amgen, BMS, GSK, Merck, Novartis and Roche. All other authors have declared no conflicts of interest.