News >

FDA Approves Two New Indications for Pembrolizumab in Advanced Melanoma

Jason M. Broderick @jasoncology
Published: Friday, Dec 18, 2015

For the second new indication, the KEYNOTE-002 study enrolled 540 patients with ipilimumab-refractory advanced melanoma. A majority of patients enrolled (83%) had M1c disease and 73% had received at least 2 prior systemic therapies.

Patients received pembrolizumab at 2 mg/kg (n = 180), 10 mg/kg (n = 181), or chemotherapy (n = 179). The chemotherapy utilized was investigator's choice and consisted primary of paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or temozolomide. Pembrolizumab was administered every 3 weeks.

The coprimary endpoints of the study were PFS and OS. The secondary endpoints of the study focused on ORR, duration of response (DOR), and safety, with responses assessed using RECIST 1.1 criteria.

Overall, following 410 PFS events, the risk of disease progression or death was reduced by 43% with pembrolizumab at 2 mg/kg (HR, 0.57; 95% CI 0.45–0.73; P <.0001) and 50% with pembrolizumab at 10 mg/kg (HR, 0.50; 0.39–0.64; P<.0001), compared with chemotherapy. Six-month PFS rates were 34%, 38%, and 16%, respectfully, with 9-month PFS rates of 24%, 29%, and 8%. 

At the 2-mg/kg dose, the ORR with pembrolizumab was 21% with a median DOR not yet reached. At the analysis, 92% of responses were ongoing. In the 10-mg/kg arm, the ORR was 25% (DOR not yet reached) and 87% of patients remained in response. A statistical different in DOR was not seen between pembrolizumab arms (P = .21).

The ORR in the chemotherapy arm was 4%, the median DOR was 37 weeks, and 63% of responses were ongoing at the time of the analysis.

Treatment-related grade 3/4 AEs occurred in 11% of patients treated with the 2-mg/kg dose, 14% with 10-mg/kg, and 26% with chemotherapy.

The most frequently occurring grade 3/4 treatment-related AEs in the 2 mg/kg pembrolizumab group were fatigue, generalized edema, and myalgia (1% each). In the 10-mg/kg arm, the most common grade 3/4 AEs were hypopituitarism, colitis, diarrhea, decreased appetite, hyponatremia, and pneumonitis (1% each). 

Among patients receiving chemotherapy, the grade 3/4 AEs most frequently observed were anemia (5%), fatigue (5%), neutropenia (4%), and leucopenia (4%).

The rates of serious adverse events were 8%, 11%, and 11%, respectively. Treatment discontinuation as a result of adverse events occurred in 3% of patients treated with the 2-mg/kg dose, 7% with 10-mg/kg, and 6% in those receiving chemotherapy. One treatment-related death was reported in the 2-mg/kg pembrolizumab arm compared with none with chemotherapy.

Pembrolizumab was previously approved by the FDA for patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

In November, the FDA approved the PD-1 inhibitor nivolumab (Opdivo) for the frontline treatment of patients with BRAF wild-type advanced melanoma. A supplemental application was also submitted to the FDA for frontline nivolumab in patients with BRAF V600 mutation–positive advanced melanoma; however, in November, the FDA issued a complete response letter to the manufacturer, Bristol-Myers Squibb, informing the company that additional data were needed for the application.


  1. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521-2532.
  2. Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908-918. 

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
35th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow® Clinical Vignette SeriesJan 31, 20192.0
Publication Bottom Border
Border Publication