The Food and Drug Administration has cleared Merck & Co.’s immunotherapy Keytruda to treat early cases of lung cancer despite mixed results in the main study supporting its application.
The regulator on Thursday approved Keytruda as an “adjuvant” treatment following chemotherapy and surgical removal of non-small cell lung tumors classified as either Stage IB, II, or IIIA. Notably, Keytruda was OK’d for broad use, regardless of the amount of a protein biomarker called PD-L1 that’s expressed on patients’ tumors.
The approval is the latest step in drugmakers’ efforts to make cancer immunotherapies — already go-to treatments for dozens of metastatic tumors — standard in earlier cancer treatment. Over the last few years, several immunotherapies have been cleared before or after surgical removal of a tumor in cancers of the skin, kidney, lung and breast.
In these settings, treatment is meant to delay cancer’s return, when it can become more lethal. They’re also large market opportunities for drug developers. Last year, analysts with SVB Securities estimated that more than half of Keytruda’s revenue growth through 2025 would come from its use as an early-stage treatment.
Lung cancer is a particularly significant market, as it remains one of the leading causes of cancer death. Though lower smoking rates have led to recent declines in lung cancer prevalence, it is still projected to account for the most cancer deaths in 2023, according to the American Cancer Society. Studies have shown anywhere from about a third to more than half of non-small cell lung cancer patients who have their tumors surgically removed later experience a recurrence.
Drugmakers and doctors hope medicines like Keytruda can help, though the treatments haven’t yet been proven to extend patients’ lives when given as an adjuvant therapy.
Merck’s drug joins Bristol Myers Squibb’s Opdivo and Roche’s Tecentriq as approved treatments for patients with early-stage lung cancer. Each is used slightly differently, though. Opdivo is given alongside chemotherapy for nine weeks before surgery, while Roche’s and Merck’s drugs involve much longer regimens following surgery.
It’s not yet clear which strategy is more effective. Results from Bristol Myers’ Opdivo trial led some experts interviewed by BioPharma Dive to favor earlier treatment, although comparing study results can be challenging. Opdivo led to a 37% average reduction in the risk of relapse or death in all patients, regardless of PD-L1 levels. By comparison, Tecentriq was associated with a 21% risk reduction in all patients and 34% in those expressing at least some PD-L1.
Among all patients in Merck’s study, Keytruda’s risk reduction was 27%. But in a result that puzzled some experts, it didn’t meet statistical significance among those with high PD-L1 expression. That, combined with an earlier FDA decision to limit Tecentriq’s approval to patients most likely to benefit, makes the broad label the FDA granted Keytruda a “positive surprise” for Merck, according to SVB analyst Daina Graybosch.
“Given this history, we were uncertain what regulators would do with the … data and [Keytruda’s] label,” Graybosch wrote in a client note. She now expects the drug “to be a very strong competitor” in adjuvant non-small cell lung cancer given the approval and its “established leadership status” in metastatic disease.
The only limitation is that patients must have already received adjuvant chemotherapy, even though Merck’s trial included some patients who hadn’t gotten chemo.