KEYNOTE-001: Findings support pembrolizumab in melanoma

Source: Healio.com/Hematology, June 2015

CHICAGO — Long-term study data confirm the durable antitumor activity associated with the anti–PD-1 antibody pembrolizumab in patients with melanoma, according to study results presented at the ASCO Annual Meeting.

Adil Daud, MD, director of melanoma clinical research at the UCSF Helen Diller Family Comprehensive Cancer Center, presented data on the long-term follow-up of 342 patients who were previously treated with ipilimumab (Yervoy, Bristol-Myers Squibb) and 313 ipilimumab-naive patients who were enrolled in the KEYNOTE-001 study.

Eligible participants received 2 mg/kg pembrolizumab (Keytruda, Merck) every 3 weeks, 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks until progression, unacceptable toxicity or the investigator made a clinical decision to stop treatment.

Researchers followed patients every 12 weeks for response rates and every 3 months for survival after treatment had been discontinued.

Objective response rate (ORR) — determined by central review per RECIST criteria — served as the primary outcome measure. PFS, OS and duration of response served as secondary endpoints.

Median follow-up was 14.8 months (range, 7.5-29).

Efficacy results indicated that 71% of the overall cohort experienced tumor shrinkage, according to Daud. The ORR was 33% and the complete response rate was 13.5% (95% CI, 8.2-20.5).

Among patients treated as first-line therapy, the ORR was 45.1% (95% CI, 36.5-54.0) and the complete response rate was 14%. Daud added that a high ORR occurred in patients with BRAF V600 mutations and wild-type BRAF.

Long-term follow-up results also demonstrated a median PFS duration of 13.8 months and a median OS of 31.1 months in the entire cohort.

“To my knowledge, this is a new high,” Daud said.

The median duration of response was 28.2 months.

“Typical of pembrolizumab, this is a prolonged response duration,” Daud said.

At 2 years, the survival rate for the full cohort was 60%.

The adverse event profile results indicated that 83% of the overall cohort experienced a treatment-related event. The rates for adverse events were 82% in the treatment-experienced group and 85% in the treatment-naive group. The most common events were thyroid events, Daud said. Pneumonitis and colitis also occurred frequently.

Disclosure: Daud reports stock ownership in, consultant/advisory roles with and research funding from Genentech/Roche, GlaxoSmithKline, Merck, OncoSec and Pfizer. Please see the abstract for a full list of the researchers’ relevant financial disclosures.

Perspective

This study confirms the durability of responses seen with pembrolizumab in melanoma.  The median survival is of course impressive. Survival of 60% at 2 years is quite significant. Persistent benefit at longer follow-up confirms the effectiveness of this agent.  Similar effectiveness with or without prior ipilimumab supports the idea of first-line use of pembrolizumab.  However, results of head-to-head sequencing trials are needed before firm conclusions can be reached.
Sanjay Awasthi, MD
City of Hope