Sandip P. Patel, MD
Immunotherapy’s introduction into the field of non–small cell lung cancer has revolutionized the treatment landscape, most recently following the phase III results of clinical trials such as PACIFIC and KEYNOTE-189, said Sandip P. Patel, MD. Yet, clinicians are working to refine existing and emerging immunologic agents.
“Bringing these therapies into the first-line metastatic setting and second-line space with the potential of durable remissions, and some patients potentially living years on these therapies with metastatic disease, has transformed medical oncology—in particular NSCLC,” explained Patel. A lot of drug development will be looking at novel combinatorial strategies to better improve outcomes for patients.”
He added that there are novel strategies that are also beginning to show signs of efficacy, including targeting NKTR-214, CSF1R, and OX40.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Non–Small Cell Lung Cancer, Patel, a medical oncologist and assistant professor of medicine at the University of California, San Diego, discussed existing and emerging immunotherapy approaches for patients with locally advanced and metastatic NSCLC.
OncLive: Please provide an overview of your presentation.
Cancer immunotherapy has revolutionized a variety of different cancers, including NSCLC. There is a wealth of options for our patients. Historically, these options had been chemotherapy. In the age of immunotherapy, including anti–PD-1 agents, we see a variety of different therapeutics in different disease stages.
In the stage III setting of NSCLC, durvalumab (Imfinzi) can be used as per the PACIFIC study, which showed that patients can receive 1 year of durvalumab consolidation therapy after chemoradiation. This is an FDA-approved regimen that looks highly effective.
In the metastatic setting, there are a variety of different options in the frontline and second-line settings. In the first-line space, we recently saw data from the KEYNOTE-189 study combining carboplatin, pemetrexed, and pembrolizumab (Keytruda) followed by pemetrexed and pembrolizumab maintenance. There was an OS benefit whether patients had greater than 50%, greater than 1%, or even less than 1% PD-L1 expression. This has become one of the standard FDA-approved regimens in the frontline space for nonsquamous NSCLC.
For patients who have PD-L1 expression greater than 50%, there remains a question as to whether pembrolizumab monotherapy or chemotherapy with pembrolizumab is the ideal combination. This is one of the questions we'll be answering over the next several years in terms of optimal sequencing.
In terms of refractory NSCLC in patients who have received frontline chemotherapy, there are 3 different options with nivolumab (Opdivo), pembrolizumab, and atezolizumab (Tecentriq). Now, we [also] have the ability to use immunotherapy to treat patients with stage III NSCLC [with durvalumab].
How do you determine what therapy to give patients with PD-L1 expression?
For patients with greater than 50% PD-L1 expression, the question [remains] whether these patients are better served by pembrolizumab monotherapy in the first-line metastatic setting or [a combination of] carboplatin, pemetrexed, and pembrolizumab.
Based on current data, my practice for more indolent, asymptomatic disease has been to do a trial of pembrolizumab monotherapy by itself for patients with greater than 50% PD-L1 expression. For patients with a visceral crisis that is highly symptomatic from their bulky disease, I'll typically utilize carboplatin, pemetrexed, and pembrolizumab because the time to response is about 2 months less in that population.
What are your thoughts on the IMpower150 study findings?
The IMpower150 trial [examined regimens involving] carboplatin, paclitaxel, bevacizumab (Avastin), and atezolizumab. It’s a 3-arm study. The data we have seen is the atezolizumab quadruplet compared with carboplatin, paclitaxel, and bevacizumab. In this study, there was improved progression-free survival (PFS) for patients who received the quadruplet. One of the most interesting things about this study was that patients with EGFR mutations or ALK rearrangements seemed to have a similar PFS benefit as the remainder of the treated population.