Tecentriq, Cabometyx May Not Improve Survival Over Chemo in NSCLC

Patients with non-small cell lung cancer (NSCLC) who do not respond to immunotherapy or whose disease progressed after treatment via immunotherapy face an unmet need, as one expert explained.

“Unless we have special pill therapies for subtypes of lung cancer with particular mutations, the vast majority of patients will start treatment with chemotherapy and immunotherapy. Sometimes those are highly effective, but oftentimes the tumors progress at some point after those therapies,” said Dr. Joel Neal, associate professor of medicine, Division of Oncology at Stanford University.

“[In] the second line setting — we call it second line because patients have already gotten the first treatments of chemo and immunotherapy — there have been many clinical trials, but there's really an unmet need for something better,” said Neal. “The one drug that's approved in this setting is [a chemotherapy] called docetaxel. It has a lot of side effects. It has neuropathy, numbness and tingling, it has low blood counts. Sometimes infections as a result of that, oftentimes hair loss depending on how the dosing is given. But it remains the FDA-approved treatment in that second line setting for non-small cell lung cancer, sometimes in combination with another IV treatment called [Cyramza (ramucirumab)] [a monoclonal antibody].”

Neal was among the international lead investigators of a study comparing the monoclonal antibody Tecentriq (atezolizumab) plus Cabometyx (cabozantinib) versus docetaxel among patients with metastatic NSCLC whose disease progressed following concurrent or sequential treatment with anti–PD-L1/PD-1 and platinum-containing chemotherapy.

Tecentriq, according to the National Cancer Institute, prevents cancer cells from suppressing the immune system, clearing the way for the immune system to fight cancer, while Cabometyx prevents cancer cells from growing and spreading.

At a minimum follow-up of 10.9 months, the median overall survival (the time a patient lives following treatment, regardless of disease status) was 10.7 months for the 186 patients in the investigational arm and 10.5 months for the 180 patients who received the standard of care, according to study findings published in the Journal of Clinical Oncology. There was no statistically significant difference between these two median survival times.

“That doesn't mean that the treatment that we were investigating wasn't effective, it just means it wasn't more effective than the current standard of care,” explained Neal. “And that meant that it could not be approved.”

The median progression-free survival times (the time a patient lives without their disease spreading or worsening) were 4.6 months and four months, respectively.

“The progression-free survival was actually a little bit better and significantly different for the investigational therapy,” Neal said. “We also looked at subsets of patients. We found that women actually did a little better with docetaxel, which was surprising, it hadn't really been seen before. Whereas men, especially men with a smoking history and cancer that was called squamous non-small cell lung cancer did significantly better with the [Cabometyx]-containing treatment.”

Serious side effects occurred in 71 patients (38.4% of patients) and 58 patients (34.7% of patients), respectively, with grade 3/4 treatment-related side effects occurring in 73 patients (39.5% of patients) and 58 patients (34.7% of patients), respectively. Death occurred in 14 patients (7.6% of patients) and 10 patients (6% of patients), and was treatment-related in four patients (2.2% of patients) and one patient (0.6% of patients), respectively, according to study findings.

“I believe that [Cabometyx] is an effective drug in non-small cell lung cancer, [but] it's probably effective for a small population of patients though,” said Neal. “And when we do big, big studies like this in a large, unselected population of patients, it's really hard to see that benefit that we see in small populations. So research is still ongoing with [Cabometyx] and related molecules to see exactly what that niche population is.”

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