Immunotherapy to Have Emerging Role in Squamous Cell Lung Cancer

George R. Blumenschein, MD

Similar to other lung cancer subtypes, combination regimens—particularly with checkpoint inhibitors and chemotherapy—are showing interest for patients with squamous non—small cell lung cancer (NSCLC).

Beyond the May 2017 FDA approval of pembrolizumab (Keytruda) plus carboplatin/pemetrexed for nonsquamous patients regardless of PD-L1 status, researchers are turning their focus to immunotherapy combinations in squamous patients in ongoing clinical trials. For example, the randomized, open-label, phase III IMpower131 study is evaluating the safety and efficacy of atezolizumab (Tecentriq) in combination with carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Abraxane) versus carboplatin/nab-paclitaxel in chemotherapy-naïve patients with stage IV squamous NSCLC (NCT02367794). The trial, which has a primary endpoint of progression-free survival, is expected to enroll 1021 patients.

This immunotherapy plus chemotherapy combination is one of many being studied in squamous NSCLC. “Immunotherapy is a new option for patients and is well established,” said George R. Blumenschein, MD. “We are refining how we use it. There will be a number of additional refinements as we have the new data that will be coming forward in the next few months.”

OncLive: What did you highlight in your presentation on advanced squamous cell carcinomas?

How do you determine the sequencing of treatments for these patients?

In an interview with OncLive at the 2017 State of the Science Summit^TM on Advanced Non—Small Cell Lung Cancer, Blumenschein, a professor in the Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discussed the current treatment landscape for patients with squamous cell lung cancer.Blumenschein: I spoke about the current state of affairs regarding immunotherapy for the advancement of patients with squamous cell carcinoma of the lung. I touched on strategies for identifying patients, the activity of the approved compounds in the space, as well as potential future approaches to refine selection of patients for therapies with immunotherapy. In terms of the standard of care, what we do when patients present with newly diagnosed metastatic disease is we take into account the patient’s comorbidities. Are they candidates for immunotherapy? We also look at their PD-L1 status and whether that patient will be able to receive pembrolizumab or another option.

Is there potential for durvalumab (Imfinzi) to play a role in squamous cell carcinoma?

What is the current unmet need for patients with squamous NSCLC?

Is the future of immunotherapy likely to be with combinations?

If their comorbidities preclude treatment with immunotherapy, or they do not have the 50% tumor proportion score, then patients should review systemic chemotherapy [options]. Subsequently, for second-line therapy—provided they have no medical contraindications— patients can receive 1 of the 3 approved immunotherapy agents.Currently, it is not playing a role; although, it has recently had positive news in the adjuvant setting after patients receive concurrent chemoradiation for locally advanced NSCLC. Based on that data, I anticipate it will be utilized in that setting. There are a number of other ongoing trials with it in combination with a CTLA-4 inhibitor. We will see [what the data show], as it may become a compound that is utilized in combination in NSCLC.The most pressing unmet needs are options for patients who cannot get immunotherapy. Another unmet need is the management of patients who have progression on immunotherapy and the various tyrosine kinase inhibitors for the different translocations or mutations. How do we best serve them to continue to provide a high-level of benefit from these compounds?Immunotherapy is being inserted into various spaces in NSCLC and in numerous combinations, whether they are immunotherapy plus immunotherapy combinations or chemotherapy plus immunotherapy regimens. Different types of checkpoint inhibitors are being studied as single agents, as well.

Another question is, “How do you help with the populations that are currently not considered candidates for immunotherapy?” There will be a number of different studies that will be reported over the next 12 months in the frontline space. These will look at immunotherapy combinations, as well as chemotherapy plus immunotherapy combinations that will hope to answer this question. There will be a shift toward more utilization of immunotherapy in the frontline setting if these studies are positive—as we hope they will be.