Three years after the pembrolizumab (Keytruda) clinical trial for advanced melanoma that led to the drug's FDA approval, 40% of the patients are still alive.
Caroline Robert, MD, PhD
Three years after the pembrolizumab (Keytruda) clinical trial for advanced melanoma that led to the drug’s FDA approval, 40% of the patients are still alive, and many of the patients are in remission even after stopping treatment.1
The results from the KEYNOTE-001 study, which were presented during a presscast held in advance of the 2016 ASCO Annual Meeting, showed that 15% of the patients experienced complete remissions according to immune-related criteria (irRC) after taking the PD-1 inhibitor and that nearly 90% of these responders remain in remission. The median overall survival (OS) was 24.2 years.
The findings are raising hopes that PD-1 checkpoint blockade immunotherapies can deliver a cure for patients with the disease, researchers said during the presscast.
“These long-term data support the durable benefit of pembrolizumab and confirm its use as one of the new standards of care for patients with advanced melanoma,” said lead study author Caroline Robert, MD, PhD, head of the Dermatology Unit at the Institut Gustave-Roussy in Paris.
Robert said the results are particularly noteworthy considering that median OS for patients with advanced melanoma was less than 1 year before the introduction of checkpoint blockade immunotherapies, starting with the anti-CTLA4 antibody ipilimumab (Yervoy) in 2011.
“It’s incredibly encouraging that we could potentially see a cure in melanoma as evidenced by the very prolonged response rate and the durability of this response,” Don S. Dizon, MD, FACP, an ASCO spokesperson who served as moderator of the presscast, said in reference to the pembrolizumab data.
The FDA granted pembrolizumab an accelerated approval in melanoma in September 2014 based on response rates among a cohort of patients in the KEYNOTE-001 study. The long-term results that will be presented at ASCO this year represent the largest dataset for survival statistics for pembrolizumab, Dizon said.
The PD-1 inhibitor nivolumab (Opdivo) demonstrated a robust 5-year OS rate of 34% for heavily pretreated patients with metastatic melanoma who had not received prior ipilimumab, according to long-term findings from a single-arm phase I study presented at the 2016 AACR Annual Meeting.2
Robert, however, noted that the nivolumab trial included results for 107 patients, whereas the enrollment in KEYNOTE-001 was far higher. Median follow-up in KEYNOTE-001 was 32 months.
The phase Ib KEYNOTE-001 enrolled 655 patients with newly diagnosed and previously treated melanoma between December 2001 and September 2013. Seventy-five percent of the participants had received prior treatment including ipilimumab.
Participants were randomized to receive pembrolizumab at 1 of 3 dosing levels: 2 mg/kg or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks. Investigators determined that the optimal dose is 2 mg/kg via intravenous infusion every 3 weeks, and that is the dosing that the FDA has recommended.
The average duration of treatment was approximately 1 year. Some patients received pembrolizumab for more than 3.5 years and 18 participants are still taking the drug, Robert said.
The overall response rate was 33% by RECIST criteria including 95 patients who had a complete response (CR) by irRC. Of these patients, 61 stopped treatment after achieving a CR following a median treatment duration of 23 months. “The vast majority of them are still without treatment and [have] a complete response,” Robert said.
Overall, 73% of the responders experienced a response duration of ≥2 years, and the median duration of response was not reached. For those who reached a CR, the duration of response ranged from >17 months to >43 months.
Two patients experienced disease progression after stopping pembrolizumab treatment, and 1 of those patients has started another course of therapy with the drug with the outcome not yet known, Robert said.
The toxicity profile of pembrolizumab was manageable, and there were no new safety signals or surprises, according to Robert. She said 8% of the patients stopped treatment because of adverse events (AEs) but that there were no fatalities related to the drug. The most common AEs were fatigue (40%), itchiness (28%), and rash (23%).
Pembrolizumab also demonstrated a survival advantage in the phase III KEYNOTE-006 trial, which compared 2 pembrolizumab regimens with ipilimumab. The 1-year OS rates for the pembrolizumab arms were 74.1% and 68.4% for 10 mg/kg every 2 weeks and 3 mg/kg every 3 weeks, respectively, compared with 58.2% for ipilimumab.3
In addition to melanoma, pembrolizumab is approved for patients with nonsmall cell lung cancer and is under study in more than 12 additional tumor types including head and neck, bladder, breast, and colorectal cancers.
Robert C, Ribas A, Hamid O, et al. 3-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.J Clin Oncol. 2016 (suppl; abstr 9503).
Hodi SF, Kluger HM, Sznol M, et al. Durable, long-term survival in previously treated patients with advanced melanoma who received nivolumab monotherapy in a phase I trial. Presented at the 2016 AACR Annual Meeting; April 16-20, New Orleans, Louisiana. Abstract CT001.
Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma.N Engl J Med. 2015;372(26):2521-2532.