Lawrence E. Feldman, MD
Combinations with checkpoint inhibitors and chemotherapy have become a standard therapeutic choice for some patients with non–small cell lung cancer (NSCLC), and such regimens continue to be explored in other subtypes—showing benefit in those with high tumor mutational burden (TMB) and squamous cell disease.
“It has reached a standard of care to receive chemoimmunotherapy as a combination,” Lawrence E. Feldman, MD, said. “I think that the data with ipilimumab and nivolumab in high TMB patients is very intriguing and is something that will probably become one of the standards of care in the near future.”
Findings from the pivotal phase III CheckMate-227 trial demonstrated superior progression-free survival (PFS) with the first-line combination of nivolumab (Opdivo) and ipilimumab (Yervoy) compared with chemotherapy for patients with advanced NSCLC who have high TMB.
For years, there has been an unmet need for effective treatments for patients with squamous cell NSCLC or small cell lung cancer (SCLC), Feldman explained. However, data from the KEYNOTE-407 trial suggest that chemoimmunotherapy regimens may benefit the squamous cell lung cancer population. In October 2018, the FDA approved first-line pembrolizumab (Keytruda) combined with carboplatin and either paclitaxel or nab-paclitaxel (Abraxane) for the treatment of patients with metastatic squamous NSCLC, based on the KEYNOTE-407 findings.
Results of the study showed that combining pembrolizumab with chemotherapy reduced the risk of death by 36% versus chemotherapy alone. The median overall survival (OS) was 15.9 months (95% CI, 13.2-not evaluable) with pembrolizumab versus 11.3 months (95% CI, 9.5-14.8) with chemotherapy alone (HR, 0.64; 95% CI, 0.49-0.85; P
In an interview during the 2018 OncLive®
State of the Science SummitTM
on NSCLC, Feldman, professor of Clinical Medicine at the University of Illinois, Chicago, discussed exciting new data surrounding immunotherapy combinations in the lung cancer.
OncLive®: Please provide an overview of your presentation on immunotherapy combinations in lung cancer.
: I discussed the immunotherapy combinations, nivolumab and ipilimumab, and durvalumab (Imfinzi) and tremelimumab. I also discussed data pertaining to combinations consisting of chemotherapy and immunotherapy, particularly the KEYNOTE-189 study that was recently presented at the 2018 ASCO Annual Meeting, which showed an overall survival advantage with pembrolizumab added to carboplatin/pemetrexed compared with chemotherapy alone.
What are the combinations being evaluated in this space and what new data are being reported?
The CheckMate-026 trial retrospectively showed that when we looked at patients with high TMB versus those with low to medium TMB, the patients with high TMB had a longer PFS when they received frontline nivolumab versus chemotherapy.
The CheckMate-227 trial and the CheckMate-568 trial confirmed the finding that patients with high TMB seemed to have a longer PFS than those with low to medium TMB; those are patients who received a combination of nivolumab and ipilimumab. We don’t have overall survival (OS) comparative data, but it was announced that the combination may move forward to receive a fast-track approval by the FDA; we’re still waiting to hear about that.
There is also the combination of carboplatin/pemetrexed and pembrolizumab, and that has shown a benefit in terms of getting the combination versus chemotherapy no matter what the PD-L1 status was; any patients who had less than 1%, 1% to 49%, or greater than 50%, had benefit with the combination of chemotherapy and pembrolizumab.
Could you discuss data pertaining to the combination of durvalumab and tremelimumab?
The dosing for the combination treatment—durvalumab at 20 mg/kg every 4 weeks plus tremelimumab at 1 mg/kg—was established in a phase Ib study. Results from the trial were published in 2016, by Dr Scott Antonia, et al in the Lancet Oncology
and showed many responses to that combination that appeared to be durable.