Photo courtesy of Merck
Pembrolizumab (Keytruda)
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.
The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.
Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.
The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).
KEYNOTE-087
KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
- Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
- Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
- Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.
KEYNOTE-013
KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.
Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.
The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.
The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.
The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.
The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.
The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).
The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).
AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.
