For More Lung Cancer Patients, the Promise of No Chemo Looms Larger

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IMPower150’s four-drug combo led to a median overall survival benefit of 19.2 months, versus 14.4 months for Avastin plus chemo. (Updated OS details won’t emerge until the American Society of Clinical Oncology conference in June, according to a spokeswoman.)

Here’s what’s new at AACR this week: Roche is revealing how patients with varying levels of PD-L1 fared in the study. Patients with higher PD-L1 levels had better results, although Roche used two different tests to measure PD-L1 levels, with slightly different readings, which underscores how PD-L1 readings are not black-and-white.

That said, the benefits for people with less than 1 percent PD-L1 levels were minimal: either a 0.2-month or 1.2-month difference in PFS. For those with the highest PD-L1 levels, the immunotherapy combination provided a 2.9 month or 5.8 month PFS difference, depending on the PD-L1 test.

With one diagnostic, for instance, Roche’s regimen kept cancers in check 12.6 months for patients with at least 50 percent PD-L1 compared to 6.8 months for Avastin plus chemo (the results were 9.1 months to 6.9 months, comparatively, using the other test).

That seems encouraging for Roche, but Merck has beaten it to the punch. As already noted, pembrolizumab without chemo is already approved for high PD-L1 patients, and the top-line Keynote-042 results Merck announced last week have experts wondering if pembrolizumab alone will have significant benefit for all patients in this area, regardless of PD-L1 status.

While options with fewer agents and potentially less toxicity look promising, Roche’s four-drug regimen uses paclitaxel, which gives pause to specialists such as Young Kwang Chae, co-director of the clinical trials unit at the Lurie Cancer Center in Chicago, because of side effects like peripheral neuropathy. And bevacizumab, which causes people to cough up blood, can be tough to deal with as well. The Keynote-189 and Checkmate-227 regimens don’t use paclitaxel or bevacizumab, and Bristol’s combo doesn’t use chemo at all.

IMpower150 investigator Mark Socinski, the executive medical director of the Florida Hospital Cancer Institute, says the Roche regimen could be for those who can handle bevacizumab. “It’s not a drug for everybody,” Socinski says, but “I think there’s a role for it.” Other specialists have also noted the IMPower150 regimen has shown some benefit for patients with a mutation in the EGFR gene who haven’t fared well on targeted drugs like erlotinib.

Still, Chow of the Seattle Cancer Care Alliance thinks the combo’s high costs will be problematic: “I don’t think most insurance companies are going to be on board with this, even if it does get FDA approved,” Her group tends not to use either paclitaxel or bevacizumab for NSCLC because of their side effects.

All the regimens are going to be expensive, says Socinski. One next step to control costs, he says, should be to figure out how to reduce unnecessary doses. Some patients have stopped taking immunotherapies because of side effects, but their responses have continued anyway. “Does [immunotherapy] really need to be given as frequently as it is?” he says. “We haven’t put a lot of effort into studying that aspect.”

Image of lung cancer metastasis courtesy of the National Cancer Institute.

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