Benjamin P. Levy, MD
Researchers are looking to further improve outcomes in non–small cell lung cancer (NSCLC) through a novel regimen of immunotherapy, angiogenesis inhibition, and chemotherapy—a synergistic combination that Benjamin P. Levy, MD, says would be exciting to have in the landscape.
The IMpower150 trial has investigated the combinatory use of antiangiogenic drugs and immunotherapy, regardless of PD-L1 expression, to improve progression-free survival (PFS), response rates, and overall survival (OS). The addition of atezolizumab (Tecentriq) to bevacizumab (Avastin), carboplatin, and paclitaxel was found to delay disease progression or death by 38% compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous NSCLC.1
“There is a lot of biological rationale why adding immunotherapy to an antiangiogenic drug such as bevacizumab may have synergy,” said Levy. “Antiangiogenic therapies can help T-cell trafficking and T-cell mobilization into the tumor microenvironment.”
Additionally, the phase III KEYNOTE-189 trial has suggested pembrolizumab’s (Keytruda) PFS and OS benefit in combination with chemotherapy. KEYNOTE-189 served as the confirmatory trial for the accelerated approval of pembrolizumab plus carboplatin/pemetrexed in the frontline setting for patients with NSCLC, regardless of PD-L1 expression. The approval was based on phase II data from cohort G of the KEYNOTE-021 trial.2
In an interview with OncLive,
Levy, assistant professor of oncology, clinical director, Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Sibley Memorial Hospital, expanded on these strategies and highlighted other trials that continue to shape the treatment landscape for patients with lung cancer.
OncLive: Can you discuss the data we have with frontline pembrolizumab and chemotherapy from the KEYNOTE-189 trial?
What we know right now is that single-agent pembrolizumab is the standard of care for patients with a PD-L1 score greater than 50% in advanced-staged patients. However, there are new data emerging from KEYNOTE-189, which is a randomized phase III trial comparing carboplatin/pemetrexed versus carboplatin/pemetrexed with the addition of pembrolizumab.
What we have heard from a news report is that there are early signals of an OS advantage for adding pembrolizumab in combination with chemotherapy. This builds on a smaller, randomized phase II trial: cohort G of the KEYNOTE-021 trial. Similarly designed, this trial tested carboplatin/pemetrexed versus carboplatin/pemetrexed with pembrolizumab. In that trial of 120 patients, we saw an improvement in response rate, an improvement in PFS, and early signals of an improvement in OS. It will be interesting to see the results from the phase III trial.
They are likely to be presented at either the 2018 AACR Annual Meeting or the 2018 ASCO Annual Meeting. In that trial, I’m interested to see the outcomes for the patients who had a PD-L1 score greater than 50% and the outcomes for the patients who had a PD-L1 score less than 50%. For the right patients, having these drugs available as single agents in the chemotherapy-refractory and upfront settings is going to be beneficial. We're all very interested and excited to see the data as they unfold.
What other combination regimens are showing promise?
The IMpower150 trial is a 3-arm trial that has been recently presented but not yet published, looking at the standard regimen of carboplatin/paclitaxel and bevacizumab (Avastin) as the control arm. This was compared to 2 other arms: carboplatin/paclitaxel and bevacizumab with atezolizumab, and carboplatin/paclitaxel and atezolizumab alone. The first analysis compared the ECOG-4599 standard of carboplatin/paclitaxel and bevacizumab to carboplatin/paclitaxel, and bevacizumab with atezolizumab.
What we saw in the data that were presented at the 2017 ESMO Immuno-Oncology Congress, was an improvement in PFS, response rates, and early signals for OS in the intention-to-treat analysis. That benefit was also seen in the patients who were PD-L1 negative. It’s a 4-drug combination, and the jury is still out on how we'll use this. However, it is exciting to see that adding another drug to an existing 3-drug regimen, specifically atezolizumab, may benefit patients.