Keytruda added to chemo slows ovarian cancer growth: Phase 3 trial
But no gains seen in patients' overall survival with combination treatment
Adding Keytruda (pembrolizumab) to chemotherapy, followed by maintenance treatment with Lynparza (olaparib), delayed cancer progression more effectively than chemotherapy alone in women with advanced ovarian cancer without BRCA mutations.
That’s according to data from the KEYLYNK-001 (NCT03740165) study, a Phase 3 clinical trial into how well Keytruda works when combined with paclitaxel and carboplatin — followed by maintenance with Lynparza, with or without bevacizumab (sold as Avastin, among other names) — as a first-line treatment for advanced ovarian cancer.
However, the combination treatment did not improve overall survival, meaning it failed to extend patients’ lives. The company plans to detail trial findings at medical meetings and to discuss them with regulators, as Keytruda’s role with these patients “remains uncertain at this time,” Merck, which markets the therapy, stated in a company press release.
“KEYLYNK-001 is the first positive Phase 3 trial for Keytruda plus Lynparza, highlighting our commitment to research that may help address the global impact of women’s cancers,” said Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories.
Clinical trial assessed Keytruda’s addition in 2 groups of ovarian cancer patients
A gynecological cancer, ovarian cancer often starts in the fallopian tubes or on the surface of the ovaries. It’s challenging to treat, especially when diagnosed at advanced stages. Patients whose tumors lack BRCA mutations face even more constraints in treatment choices, as BRCA mutations are known to elevate cancer risk and can inform targeted therapy decisions.
Keytruda, an immunotherapy, is approved to treat over a dozen types of cancer, but not ovarian cancer. “For people living with ovarian cancer, there remains an unmet need for new treatment options that have the potential to improve outcomes,” Aktan said.
The global KEYLINK-001 trial randomly assigned 1,367 women with advanced ovarian cancer to one of three treatments. A first patient group received infusions of Keytruda and chemotherapy, followed by maintenance treatment with Keytruda plus oral Lynparza. The second group received Keytruda with chemotherapy, followed by Keytruda plus an oral placebo. The third was treated with chemotherapy and given a placebo.
Administered via an infusion every three weeks, Keytruda works by binding to an immune checkpoint protein called PD-1, which cancer cells use to prevent the immune system from mounting a response against them. By blocking that protein, immune cells can come closer to cancer cells, with a goal of more effectively killing them.
Lynparza, approved to treat advanced ovarian cancer, works by preventing cancer cells from repairing their DNA, leading to their death. Some patients also were given bevacizumab, which works to limit the formation of new blood vessels. Cancer cells are fast-growing cells, and they need blood vessels to receive oxygen and nutrients for growth.
Better overall survival with Keytruda was a key secondary trial goal
KEYLINK-001’s main goal was to see if the combination treatment could delay cancer progression by watching for changes in progression-free survival for up to 57 months, about 4.7 years. Data showed that it was more effective at controlling the cancer for a longer time than chemotherapy alone.
“The KEYTRUDA plus LYNPARZA regimen demonstrated a statistically significant and clinically meaningful improvement in PFS [progression-free survival] for these patients” relative to chemotherapy only, Merck reported.
However, the trial did not meet a key secondary goal of better overall survival, which measures how long patients live after starting treatment. This raises questions about the long-term benefit of the combination treatment for these patients.
The safety profiles of Keytruda and Lynparza were consistent with those reported for each therapy in previous studies, with no new safety concerns identified.
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