First-line treatment with Keytruda (pembrolizumab) and chemotherapy prolongs the time without disease worsening in people with advanced triple-negative breast cancer (TNBC) whose tumors are positive for the marker PD-L1, an interim analysis of the KEYNOTE-355 trial shows.
The analysis, conducted by an independent committee, confirmed that one of the trial’s primary goals was met — time to disease progression or death increased significantly and in a clinically meaningful way, compared to chemotherapy alone, in patients with PD-L1 in more than 10% of the cells in their tumors (including tumor cells and immune cells).
Keytruda’s safety profile remains consistent with prior studies, and no new safety signals were observed.
Based on the committee’s recommendation, KEYNOTE-355 will continue as planned to evaluate other primary and secondary trial measures.
“Triple-negative breast cancer is an aggressive malignancy. It is very encouraging that Keytruda in combination with chemotherapy has now demonstrated positive results as both a first-line treatment in the metastatic setting with this trial, and as neoadjuvant therapy in the KEYNOTE-522 trial,” Roger M. Perlmutter, president of Merck Research Laboratories, said in a press release.
“We look forward to sharing these findings with the medical community at an upcoming congress and discussing them with the FDA and other regulatory authorities,” Perlmutter added.
KEYNOTE-355 (NCT02819518) is a randomized Phase 3 trial evaluating the safety and efficacy of Keytruda in combination with one of three chemotherapies — Abraxane (nab-paclitaxel), Taxol (paclitaxel) or Gemzar/Paraplatin (gemcitabine/carboplatin) — compared to placebo plus chemotherapy in treating patients with locally recurrent and inoperable or metastatic TNBC.
The trial has two parts: a first part evaluated the safety and tolerability of Keytruda’s combo in 30 patients; the second is determining its two primary efficacy outcomes — overall survival and time to disease worsening or death (a measure called progression-free survival) — in 847 patients.
In this second part, patients were randomized to Keytruda, given by into-the-vein (intravenous) infusions on day one of each 21-day cycle, in combination with one of the three chemotherapy options or to a placebo plus one of those chemotherapy regimens.
Both primary endpoints — overall survival and progression-free survival — will be determined for all participants and for the subgroup of patients whose tumors are positive for PD-L1, the cancer marker whose signals are blocked by Keytruda.
Two subgroups of patients with PD-L1 positive tumors are being examined, those with at least 1% of cells producing the factor, and those in which 10% or more cells in their tumors produce PD-L1.
Other secondary measures include the percentage of patients responding well to treatment (objective response rate, ORR), duration of response, disease control rate, and quality of life measures in the overall population and in the two PD-L1 positive subgroups. Safety is also being examined.
Keytruda is an immune checkpoint inhibitor, developed by Merck (known as MSD outside the U.S. and Canada), designed to enhance the body’s natural immune response against cancer. It is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat several types of cancer.
It is an antibody that targets and blocks the activity of PD-1, a protein found on the surface of immune cells that acts as a type of “off switch” to keep immune cells from attacking other cells.
PD-1 naturally binds to PD-L1, a protein found on all cells but in higher-than-normal amounts on some types of cancer cells, and these cancers are known to use this interaction to fend off immune attacks.
By blocking PD-1, Keytruda prevents this communication, releasing the “brakes” on the immune system and leaving it more free to kill cancer cells.
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