The rapidly changing treatment landscape for lung cancer could soon change again.
This morning, Merck (NYSE: MRK) announced that a Phase 3 study called Keynote-407 has succeeded. The trial tested a combination of its immunotherapy pembrolizumab (Keytruda) and chemotherapy in 560 patients just diagnosed with advanced, squamous non-small cell lung cancer. Merck didn’t disclose specifics, but said that upon an interim look at the study, the pembro-chemo combination extended patients’ lives and kept cancer from spreading “significantly longer” than chemotherapy alone.
Merck has already submitted the data to regulators, and will divulge more data at next month’s big American Society of Clinical Oncology meeting (ASCO). In an ASCO abstract posted last week, Merck said 58 percent of pembro-chemo patients responded to treatment compared to 35 percent for those on chemo alone.
Lung cancer remains by far the leading cause of cancer death. An estimated 154,050 people are expected to die from the disease in 2018, according to the American Cancer Society. NSCLC is the most common form of lung cancer, representing about 85 percent of all cases, and about 25 to 30 percent of them have the more aggressive, “squamous” form, according the ACS.
For decades, chemotherapy was the main option for patients with advanced lung cancer. Then came targeted therapies, which home in on genetic mutations like ALK and EGFR. But most patients don’t have these mutations, and immunotherapy has begun over the past few years to make its mark in the large remaining pool.
The FDA approved both pembrolizumab and Bristol-Myers Squibb’s (NYSE: BMY) nivolumab in October 2015 for patients whose NSCLC had spread after chemotherapy. Then in 2016, pembrolizumab succeeded in a Phase 3 trial in newly diagnosed advanced NSCLC patients, but nivolumab failed. Pembrolizumab became the first FDA-approved immunotherapy to treat a portion of newly diagnosed lung cancer patients. Merck followed with an FDA approval of pembrolizumab plus chemotherapy in newly diagnosed patients.
This year the pace of change has quickened. Merck disclosed in April that advanced NSCLC patients receiving just pembrolizumab lived much longer than those on chemotherapy in its Keynote-042 study. (Details from that highly anticipated trial are expected at ASCO). And at the American Academy of Cancer Research’s (AACR) annual meeting in April, Merck, Bristol-Myers, and Roche all presented updates from studies of regimens that combined immunotherapies with other treatments.
Taken together, the updates at AACR advanced immunotherapy as an option for bigger swaths of lung cancer patients. The pembro-chemo combination, for example, cut the risk of death or worsening disease in half compared to chemo alone in advanced NSCLC patients. A combination of Bristol’s two immunotherapies, nivolumab and ipilimumab (Yervoy), helped a subset of NSCLC patients whose tumors have unusually high levels of genetic mutations, known as tumor mutational burden. A Roche regimen that included chemotherapy, its immunotherapy atezolizumab (Tecentriq), and bevacizumab (Avastin), was better than the same regimen without immunotherapy.
That brings us to Keynote-407, which is the first Phase 3 study to show that immunotherapy and chemo are better than chemo alone specifically for squamous NSCLC patients. Though the magnitude of the benefit seen is not yet clear, a big impact on the disease could further solidify the pembro-chemo regimen as a standard for advanced lung cancer.
Lung cancer image by the National Cancer Institute