Merck's Keytruda makes the cut as a second-line monotherapy for certain esophageal cancer patients
Merck’s cornerstone checkpoint inhibitor Keytruda has added another jewel to its crown.
The US drugmaker on Wednesday disclosed that the PD-1 drug had won approval as a monotherapy for patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus, whose tumors express PD-L1, and whose disease has progressed despite one or more prior lines of systemic therapy.
About 17,650 new esophageal cancer cases will be diagnosed this year in the United States, the American Cancer Society estimates. Typically, patients with the advanced form of the disease have limited treatment options.
The approval was based on the KEYNOTE-181 study, which tested the drug versus chemotherapy in a broad group of 628 previously-treated patients with recurrent locally advanced or metastatic esophageal cancer. The main goal of the study — overall survival — was met only in a subgroup of patients, in patients whose tumors express PD-L1.
In its January update, the company said that Keytruda reduced the risk of death by 31% in patients with squamous cell carcinoma or adenocarcinoma in the study. The subgroup with PD-L1-positive patients — which constituted 222 patients — achieved a median OS of 9.3 months versus 6.7 months for the chemotherapy group. They also had a 12-month OS rate of 43% while the chemotherapy arm experienced 20%.
However, for the intention-to-treat population, the difference in OS between the two arms was not statistically significant. In the 401 patient subgroup of squamous cell carcinoma patients, the Keytruda group experienced a median OS of 8.2 months, compared to 7.1 months for the chemotherapy arm — another non-statistically significant difference.
Data from the KEYNOTE-180 study, which included 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease, also contributed to the approval, Merck said.
Merck $MRK is also running a separate Phase III study — dubbed KEYNOTE-590 — pitting Keytruda in combination with chemotherapy as a first-line treatment in patients with esophageal carcinoma. The trial is expected to wrap up next month.
Keytruda, which is approved for a plethora of cancers, has cemented its crown in the field of immuno-oncology. It generated $2.6 billion in second-quarter revenue, up 58% over the same period a year ago.
The drug is on track to eclipse $10.6 billion in sales by the end of the year — which is more than 50% over what it generated in 2018 — and to surpass $20 billion by 2024, Mizuho analysts wrote in a note.
Keytruda was once seen as an underdog to Bristol-Myers’ pioneering Opdivo, but a string of trial failures left Opdivo in the backseat and Keytruda as the driving force. Now, some worry that Merck may be leaning too heavily on its keystone asset, but the company’s R&D chief Roger Perlmutter is working on buttressing the company’s pipeline with a string of acquisitions to mitigate those concerns.
“While KEYTRUDA is growing in dominance, both in the market and on MRK’s P&L, we see MRK as having considerable runway (2028 LOE) to address concerns regarding concentration of revenue,” Mizuho analysts added.
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