Merck & Co. announced Sunday that in the Phase III KEYNOTE-522 trial, pathological complete response (pCR) in patients with early triple-negative breast cancer (TNBC) significantly increased from 51.2% in the placebo plus chemotherapy group to 64.8% in those given Keytruda (pembrolizumab) in combination with chemotherapy. Study author Peter Schmid said "we found a 13.6% difference which is a clinically meaningful benefit" when Keytruda was added to chemotherapy prior to surgery.
In July, Merck reported that the trial met its primary endpoint of pCR, noting at the time that Keytruda is the first anti-PD-1 therapy to achieve this result as a neoadjuvant treatment for TNBC regardless of PD-L1 status. The study enrolled a total of 1174 patients, with the interim analysis presented at ESMO coming after a median follow-up of 15.5 months in the first 602 patients.
Further data showed that pCR was 68.9% for Keytruda in the PD-L1-positive population, versus 54.9% for the placebo group, while in the PD-L1-negative population, the rates of pCR were 45.3% and 30.3%, respectively. Commenting on the results for ESMO, Fabrice André noted that while a large benefit in response rates was expected, the poor predictive value of PD-L1 was surprising. "This is probably because most early-stage triple negative breast cancers express some degree of PD-L1, sometimes below the predefined cut-off of positivity."
The researchers also conducted an interim analysis of event-free survival, the trial's dual-primary endpoint, with results demonstrating "a favourable trend" for the Keytruda group with a 37% reduction in the risk of progression. At 18 months, 91.3% of patients given Keytruda were event-free, versus 85.3% of those on placebo. "These are preliminary data, but they provide a strong sign that the addition of immune therapy to neoadjuvant chemotherapy prevents breast cancer recurrence," remarked Schmid, adding "if we prevent recurrence, we cure more patients, but we need longer-term data for confirmation."
The results come after Merck announced in May that Keytruda failed to prolong OS versus chemotherapy in patients with second- or third-line metastatic TNBC in the Phase III KEYNOTE-119 trial. The company reported detailed findings from the study at ESMO, with data showing that Keytruda did not significantly improve OS in patients with a PD-L1 combined positive score (CPS) ≥10, a PD-L1 CPS ≥1 or in all subjects, although the treatment effect of the drug increased in line with CPS. In an exploratory analysis of patients with a PD-L1 CPS ≥20, median OS was 14.9 months for Keytruda, compared to 12.5 months for chemotherapy.
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