Claude Denham, MD
Immunotherapy continues to establish itself in the treatment of patients with non–small cell lung cancer (NSCLC), yet physicians continue to face challenges in later-line settings with resistance, hyperprogression, and optimal responders.
The second-line PD-1/PD-L1 agents in the landscape include nivolumab (Opdivo), pembrolizumab (Keytruda), and atezolizumab (Tecentriq) for patients who progress on platinum-based chemotherapy. The FDA recently approved durvalumab (Imfinzi) for treating those with locally advanced, unresectable stage III disease who have not progressed following chemoradiotherapy.
Moreover, frontline pembrolizumab is also approved by the FDA for patients with metastatic NSCLC who harbor ≥50% PD-L1 expression and as a frontline treatment in combination with carboplatin/pemetrexed, regardless of PD-L1 status, for patients with advanced or metastatic nonsquamous NSCLC.
However, selecting patients for second-line immunotherapy can be challenging, says Claude Denham, MD, because PD-L1 and tumor mutation burden (TMB) are not as reliable as indicators of response. Patients with driver mutations often do not respond as well to immunotherapy in the second-line setting.
Although strides have been made in the past few years, some patients with NSCLC remain resistant to immunotherapy or potentially may experience hyperprogression. A subset of patients experience long-term remission with immunotherapy agents alone, but combinations with immunomodulatory drugs or anti–CTLA-4 agents might hold promise, says Denham.
In a presentation during the 2018 OncLive®
State of the Science Summit™ on Non–Small Cell Lung Cancer, Denham, a medical oncologist at Baylor Charles A. Sammons Cancer Center, discussed the use of immunotherapy beyond the first-line setting in NSCLC. In an interview during the event, he dove deeper into the challenges with immunotherapy in this disease, as well as the promise of combination therapy.
OncLive: Can you give an overview of your presentation?
My topic lays the groundwork for a lot of the others—it is the use of immunotherapy, largely anti–PD-1 therapy, for NSCLC. I reviewed the pivotal trials that have demonstrated that this is essentially the standard of care for most patients in the second-line setting for NSCLC, both adenocarcinoma and squamous cell carcinoma.