Keytruda Raises Hope of Conquering Advanced Melanoma

Three years after the clinical trial that led to the approval of Keytruda (pembrolizumab), 40 percent of the patients involved who had advanced melanoma are still alive. Many are even in remission and have stropped treatment.

The results from the KEYNOTE-001 study, which were presented during a presscast held in advance of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that 15 percent of the patients experienced complete remissions according to immune-related criteria (irRC) after taking the PD-1 inhibitor and that nearly 90 percent of these responders remain in remission. The median overall survival (OS) was 24.2 months.

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 Keytruda and confirm its use as one of the new standards of care for patients with advanced melanoma,” said lead study author Caroline Robert, head of the Dermatology Unit at the Institut Gustave-Roussy in Paris, France.

Robert said the results are particularly noteworthy considering that median OS for patients with advanced melanoma was less than one year before the introduction of checkpoint blockade immunotherapies, starting with the anti-CTLA—4 antibody Yervoy (ipilimumab) 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, an ASCO spokesperson who served as moderator of the presscast, said in reference to the Keytruda data.

The FDA granted Keytruda 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 Keytruda, Dizon said.

The PD-1 inhibitor Opdivo (nivolumab) demonstrated a robust five-year OS rate of 34 percent for heavily pretreated patients with metastatic melanoma who had not received prior Yervoy, according to long-term findings from a single-arm phase 1 study presented at the 2016 AACR Annual Meeting.

Robert, however, noted that the Opdivo 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 1b 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 Yervoy.

Participants were randomized to receive Keytruda at one of three dosing levels: two mg/kg or 10 mg/kg every three weeks, or 10 mg/kg every two weeks. Investigators determined that the optimal dose is two mg/kg via intravenous infusion every three weeks, and that is the dosing that the FDA has recommended.

The average duration of treatment was approximately one year. Some patients received Keytruda for more than 3.5 years and 18 participants are still taking the drug, Robert said.

The overall response rate was 33 percent 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 percent of the responders experienced a response duration of at least two 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 Keytruda treatment, and one of those patients has started another course of therapy with the drug with the outcome not yet known, Robert said.

The toxicity profile of Keytruda was manageable, and there were no new safety signals or surprises, according to Robert. She said 8 percent 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 percent), itchiness (28 percent) and rash (23 percent).

Keytruda also demonstrated a survival advantage in the phase 3 KEYNOTE-006 trial, which compared two Keytruda regimens with Yervoy. The one-year OS rates for the Keytruda arms were 74.1 percent and 68.4 percent for 10 mg/kg every two weeks and three mg/kg every three weeks, respectively, compared with 58.2 percent for Yervoy.

In addition to melanoma, Keytruda is approved for patients with non—small cell lung cancer and is under study in more than 12 additional tumor types including head and neck, bladder, breast and colorectal cancers.