Balazs Halmos, MD, MS
The addition of pembrolizumab (Keytruda) to chemotherapy should define the frontline standard of care for patients with metastatic squamous non–small cell lung cancer (NSCLC), following the results of the phase III KEYNOTE-407 trial, said Balazs Halmos, MD.
Based on KEYNOTE-407, the FDA approved pembrolizumab for use in combination with carboplatin and either paclitaxel or nab-paclitaxel (Abraxane) for the treatment of patients with metastatic squamous NSCLC.
In the study, combining pembrolizumab with chemotherapy reduced the risk of death by 36% compared with 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
= .0017). The OS benefit was observed regardless of PD-L1 expression level, choice of taxane, age, sex, and ECOG performance status.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, Halmos discussed the latest developments in the treatment paradigm for patients with squamous cell NSCLC.
OncLive: How have recent clinical trials altered the management of squamous NSCLC?
: At the meeting, I covered major advances in the management of advanced squamous cell lung cancer. This certainly has been a breakthrough year in progress for this particular subset of patients. Up until a few years ago, the standard of care had remained doublet chemotherapy for frontline management of squamous cell lung cancer. The major thing that we learned was what not to use, such as bevacizumab (Avastin) or pemetrexed.
Later on, we saw a series of positive randomized studies, such as LUX-Lung 8 and SQUIRE. These were important studies leading to FDA approvals of compounds, such as afatinib (Gilotrif), necitumumab (Portrazza), as well as ramucirumab (Cyramza). The benefit with each of those studies seemed to be small enough that enthusiasm has remained low in terms of market share for these compounds.
It's been welcoming news to see the very positive results of CheckMate-017. The trial showed a very substantial survival benefit, and not just a progression-free survival (PFS) benefit with second-line nivolumab (Opdivo) versus docetaxel. Of course, the hope was that immunotherapy could be moved into the frontline management, similar to what we've seen with nonsquamous NSCLC, especially with the KEYNOTE-189 trial.
For immunotherapy studies of both squamous and nonsquamous subsets, we've seen significant benefits in the squamous subset, such as KEYNOTE-024, which demonstrated benefit for frontline pembrolizumab versus doublet chemotherapy. Additionally, in CheckMate-227, the combination [of nivolumab and ipilimumab (Yervoy) demonstrated benefit in patients with high] tumor mutational burden. Of course, these are still preliminary data with CheckMate-227. There is no OS benefit and no FDA approval, but it’s certainly something to watch out for.
Within the last year, we've seen results from 2 pivotal studies looking at the combination of doublet chemotherapy and immunotherapy in the frontline setting. The first study, IMpower131, looked at the combination of taxane-based doublet chemotherapy plus atezolizumab (Tecentriq). Though the study had shown significant PFS benefits for the combination, it didn't translate into an OS benefit, disappointingly.
More encouragingly was the KEYNOTE-407 study, which looked at the combination of taxane-based chemotherapy with investigator’s choice of paclitaxel or nab-paclitaxel, with or without pembrolizumab. This was followed by maintenance pembrolizumab versus placebo. [The addition of pembrolizumab] showed not just a PFS benefit, but a very substantial OS benefit, as well, with an HR just around 0.6. This benefit was seen in every single PD-L1 subset.