Adding Tecentriq to Chemo Regimen Improves Lung Cancer Outcomes

Not all patients with non-small cell lung cancer (NSCLC) respond to immunotherapy, so researchers are exploring the use of combination regimens, including immune checkpoint inhibitors and chemotherapy, to improve outcomes in these patients.

“One issue about immunotherapy is that a minority of patients respond to it — that is, only about 20 percent,” Paul A. Bunn Jr, M.D., distinguished professor in the Division of Medical Oncology and the James Dudley Chair in Lung Cancer Research at the University of Colorado in Denver, said in an interview with OncLive, a sister publication of CURE.

“Therefore, we were wondering: If you combined a single-agent checkpoint inhibitor with other immunotherapies, chemotherapies or antiangiogenic agents, would you have a higher response rate and better overall outcome?”

Results from the phase 3 IMpower150 trial are helping to answer that question. The trial enrolled 1,202 patients with stage 4 nonsquamous NSCLC who were randomized to one of three arms: Tecentriq (atezolizumab) plus chemotherapy; Tecentriq in combination with Avastin (bevacizumab) plus chemotherapy; or Avastin plus carboplatin and paclitaxel.

Treatment with Tecentriq plus Avastin and chemotherapy (Arm B) delayed progression or death by 38 percent compared to Avastin and chemotherapy alone. Similarly, this arm experienced extended progression-free survival (8.3 months vs. 6.8 months, respectively).

After a minimum of 9.5 months of follow-up, the Tecentriq arm also experienced longer overall survival compared with Avastin and chemotherapy alone. (19.2 months vs. 14.4 months).

Although the trial met its primary endpoint, Bunn noted that cost may affect the regimen’s future use. “The major disadvantage is that this combination is a more expensive regimen. However, this combination is the first one to have a phase 3 trial done.”

Although other trials are evaluating Keytruda (pembrolizumab) in similar combinations to treat patients with NSCLC, this is the first trial to take a look at chemotherapy versus chemotherapy plus a checkpoint inhibitor.

While Keytruda typically targets PD-1 and PD-L1, for the IMpower trial, researchers compared the regimens for patients with T-effector gene expression signature. There were differences in results between patients who were T-effector high and T-effector low, though they were not statistically significant. “I also do not believe that anyone will decide whether to use chemotherapy plus Tecentriq or Keytruda based on a biomarker,” Bunn said.

Although a skeptic at first, Bunn believes more and more data will come out supporting the combination use of checkpoint inhibitors with chemotherapy, and after that, cross trials to compare single agents compared with these combination regimens.

“If you have PD-L1 expression greater than 50 percent, monotherapy alone does well. Again, cross trial comparisons are complicated. It is likely that in the next six months, all of these trials will report out,” he said. “…We are probably going to see an increase in first-line use of checkpoint inhibitors.”

Altogether, the future of these combinations looks promising, and how Tecentriq will be used is to be determined. “It is likely that in the future, there will be an increase in immunotherapy plus chemotherapy combinations in the first-line setting,” said Bunn. “Tecentriqis going to be used, but how often it is used still needs to be determined.”