Merck & Co. announced that positive results were presented Sunday at the European Society for Medical Oncology (ESMO) congress from two studies evaluating Keytruda (pembrolizumab) as a first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC). According to Merck, Keytruda demonstrated superior progression-free survival (PFS) and overall survival (OS) versus standard chemotherapy in the KEYNOTE-024 trial of patients whose tumours expressed high levels of PD-L1, while data from the KEYNOTE-021 study, whose participants were not selected by PD-L1 expression, showed that combining the PD-1 inhibitor with chemotherapy resulted in superior efficacy over chemotherapy alone.
Roger Perlmutter, president of Merck Research Laboratories, said the latest findings suggest Keytruda "can offer meaningful improvement over chemotherapy in a broad array of patients," adding that "in this sense, these studies may represent a turning point in worldwide efforts to control lung cancer."
The Phase III KEYNOTE-024 trial included 305 previously untreated patients with squamous or non-squamous NSCLC who had tumour proportion scores of over 50 percent, as determined by Agilent Technologies' Dako PD-L1 IHC 22C3 PharmDx companion diagnostic. Patients were randomised to receive a fixed dose of Keytruda monotherapy every three weeks or four to six cycles of one of five platinum-based chemotherapy regimens. Merck noted that control-group patients had the option of crossing over to Keytruda upon disease progression. Median follow-up was 11.2 months and the study's primary endpoint was PFS, while secondary endpoints were OS, overall response rate (ORR) and safety.
Results, which were also published in the NEJM, showed that Keytruda reduced the risk of progression or death by 50 percent compared to chemotherapy alone, with a median PFS of 10.3 months and 6 months, respectively. At six months, 62.1 percent of Keytruda-treated patients were alive and had no disease progression, compared to 50.3 percent of those in the chemotherapy group. Merck said the PD-1 inhibitor also resulted in a 40-percent reduction in the risk of death versus chemotherapy, adding that "this finding includes the 66 patients on the chemotherapy arm who crossed over in-study to receive Keytruda once their cancer had progressed." The company said median OS was not reached in either group, while ORR was 44.8 percent for patients receiving Keytruda, including six complete responses, versus 27.8 percent with chemotherapy, including one complete response. "The safety of Keytruda was consistent with what has been seen in previous trials among patients with metastatic NSCLC," Merck added.
Meanwhile, the KEYNOTE-021 study's G cohort included 123 previously untreated patients with metastatic non-squamous NSCLC, regardless of PD-L1 expression, whose tumours did not have EGFR mutations or ALK translocations. Patients were randomly assigned treatment with Keytruda plus standard chemotherapy, or standard chemotherapy alone, with those in the chemotherapy-only arm having the option to cross over to Keytruda monotherapy if their disease progressed. Median follow-up was 10.6 months.
The study, whose results were published in The Lancet Oncology, found that ORR was 55 percent among patients who received Keytruda plus chemotherapy, compared to 29 percent for chemotherapy alone, with Merck noting that all responses were partial. Median duration of response was not reached in either group, but Merck noted that 88 percent of responders in the Keytruda arm and 78 percent of responders in the chemotherapy-alone arm experienced "ongoing response at the time of data cut-off." Merck said adding Keytruda to chemotherapy also significantly reduced the risk of disease progression or death compared to chemotherapy alone, with median PFS being 13 months for the Keytruda group, versus 8.9 months for those treated with chemotherapy alone. Further, the company said OS was 92 percent at six months in both arms, while at 12 months survival was 75 percent and 72 percent in the combination and chemotherapy-alone arms, respectively.
The FDA last month granted priority review to Merck's filing seeking to expand Keytruda to include first-line use in NSCLC for patients whose tumours express PD-L1, with the regulator expected to make a decision by December 24. The PD-1 inhibitor, which was first approved in the US in 2014 for melanoma, was expanded last year for the treatment of patients with PD-L1-positive NSCLC whose disease progressed after prior treatment.
Meanwhile, Bristol-Myers Squibb presented the final primary analysis from the late-stage CheckMate -026 study at ESMO showing that its PD-1 inhibitor Opdivo (nivolumab) failed to significantly improve PFS versus chemotherapy when used in the first-line setting for advanced NSCLC patients whose PD-L1 expression was at least 1 percent. Opdivo generated global sales of $1.5 billion for the first six months of 2016, while Keytruda had sales of $563 million.
For related analysis, see ViewPoints: Could festive cheer crown 2016 as the year of Keytruda?
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