Less Is More in Lung Cancer Treatment

Less may be more in the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC), according to the results of a recent clinical trial.

“The results are significant because they show that we may not need four cycles of chemotherapy with immunotherapy to have good efficacy,” said Dr. David Carbone, a professor of medicine and director of the James Thoracic Center at The Ohio State University Wexner Medical Center in Columbus and an author on the study, in an interview with CURE®.

Carbone and colleagues recently published data that evaluated two cycles of chemotherapy — instead of the standard four cycles alone — combined with the immunotherapies Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with metastatic or recurrent NSCLC.

Data from that trial — known as CheckMate-9LA — demonstrated that treatment with Opdivo and Yervoy plus two cycles of chemotherapy reduced the risk of death among patients by 31% compared with the chemotherapy-only regimen.

Moreover, the results indicated that patients assigned to the Opdivo- Yervoy regimen had an overall median survival (defined as the time from randomization to date of death due to any cause) of 14.1 months versus the 10.7 months in the group that was given four cycles of chemotherapy alone. Overall survival was also longer in the combination group regardless of programmed death-ligand 1 levels or tumor histology (the description of the tumor’s characteristics). Overall, Carbone and colleagues noted that the longer the follow-up, the more the combination therapy seemed to improve survival rates.

Of note, these results led the Food and Drug Administration to approve the combination regimen earlier this year for the treatment of these patients.

Advantage of Less Chemo

What’s significant about the results of this trial is that not only does the combination regimen appear to improve overall survival in patients, but it also gives them a less toxic treatment option.

Recent estimates from the Centers for Disease Control and Prevention indicate that about 650,000 patients with cancer in the United States receive chemotherapy. And although chemotherapy drugs kill fast-growing cancer cells, they also come with potential debilitating side effects and toxicities such as fatigue, hair loss, nausea and anemia.

“It’s not a chemo-free regimen, but it’s only two cycles of chemo instead of four,” Carbone said regarding the Opdivo-Yervoy regimen. “People really do not like chemotherapy, and as someone who’s had chemotherapy, I know what that’s like. There is an advantage to not having (as much).”

He noted that the combination also helps patients with squamous cell cancers avoid two cycles of full-dose paclitaxel, which can be toxic. For those with non-squamous cell cancers, he mentioned that the standard treatment is the KN189 regimen, which includes the chemotherapies carboplatin and pemetrexed, as well as the immunotherapy Keytruda (pembrolizumab). During this regimen, pemetrexed is given every three weeks for two years, with steroids at every cycle. “With the standard chemotherapy-plus-Keytruda regimen, you have maintenance chemotherapy that goes on for two years, and that confers a chronic toxicity from the chemotherapy,” Carbone explained. “The (Opdivo-Yervoy regimen) eliminates all of these chemotherapy doses except for two and all of the two years of steroid doses, which might help the durability of response.”

“I think patients should be aware that it’s an available and reasonable option,” Carbone concluded, adding that there is potential to use this concept in cancer settings other than NSCLC, though that hasn’t been investigated. “It is a great time in lung cancer, but there’s still a long way to go, that’s for sure.”

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