Lecia V. Sequist, MD, MPH, the Landry Family Associate Professor of Medicine at Harvard Medical School, and director, Center for Innovation in Early Cancer Detection, Massachusetts General Hospital, discusses the use of pembrolizumab (Keytruda) monotherapy versus the combination of pembrolizumab and chemotherapy in advanced nonsquamous non—small cell lung cancer (NSCLC).

When a patient with advanced nonsquamous NSCLC presents in the clinic with a PD-L1 expression higher than 50%, the decision of whether to pursue pembrolizumab monotherapy or combination chemoimmunotherapy should be done on an individualized basis. If the patient is highly symptomatic, and a faster response is needed, the combination of chemotherapy and immunotherapy is likely the better option, as this approach has shown higher response rates compared with pembrolizumab monotherapy, explains Sequist.

Conversely, if a patient with high PD-L1 expression is not fit enough to receive a triplet regimen due to mild renal insufficiency or borderline performance status, immunotherapy alone is the optimal choice, as high PD-L1 expression is indicative of benefit from single-agent pembrolizumab.

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Lecia V. Sequist, MD, MPH, the Landry Family Associate Professor of Medicine at Harvard Medical School, and director, Center for Innovation in Early Cancer Detection, Massachusetts General Hospital, discusses the use of pembrolizumab (Keytruda) monotherapy versus the combination of pembrolizumab and chemotherapy in advanced nonsquamous non–small cell lung cancer (NSCLC).

Dr. Sequist on Pembrolizumab Monotherapy in Nonsquamous NSCLC

Lecia V. Sequist, MD, MPH, the Landry Family Associate Professor of Medicine at Harvard Medical School, and director, Center for Innovation in Early Cancer Detection, Massachusetts General Hospital, discusses the implications of the phase III IMpower150 trial in advanced nonsquamous non—small cell lung cancer (NSCLC).

There are several frontline regimens of chemotherapy and immunotherapy that are now FDA approved in the United States for nonsquamous NSCLC, the most recent of which is the 4-drug regimen composed of carboplatin, paclitaxel, bevacizumab (Avastin), and atezolizumab (Tecentriq). The approval was based on data from the IMpower150 study, which compared chemotherapy versus chemotherapy with immunotherapy. The trial also addressed the question of whether or not VEGF inhibition is needed.

The trial suggested that there might be an additive benefit with VEGF and immunotherapy, says Sequist. Notably, IMpower150 was the only study to include a subset of patients with driver mutations such as 

. The trial suggested, albeit in a small patient size, that there was a benefit to administering chemotherapy and immunotherapy in those patients. There are many interesting leads being generated from that study, adds Sequist. However, these leads need to be explored further before they can be generalized and applied to routine practice. Despite the availability of the regimen, Sequist says most practitioners are opting for 1 of the pembrolizumab (Keytruda) regimens instead because 4 drugs together can be a lot to handle.

Lecia V. Sequist, MD, MPH, the Landry Family Associate Professor of Medicine at Harvard Medical School, and director, Center for Innovation in Early Cancer Detection, Massachusetts General Hospital, discusses the implications of the phase III IMpower150 trial in advanced nonsquamous non–small cell lung cancer (NSCLC).

Dr. Sequist on Implications of the IMpower150 Trial in Advanced Nonsquamous NSCLC

Lecia V. Sequist, MD, MPH, thoracic medical oncologist and director of the Center for Innovation in Early Cancer Detection at Massachusetts General Hospital Cancer Center, discusses the rationale for the TATTON trial in non—small cell lung cancer (NSCLC).

For the phase Ib clinical trial, investigators evaluated the use of the EGFR inhibitor osimertinib (Tagrisso) plus the MET inhibitor savolitinib in patients who had EGFR-mutant NSCLC that had developed resistance to prior EGFR-targeted therapies through MET-gene amplification. 

The rationale for the study was based on findings from preclinical work which looked at MET as a resistance pathway and found that both of those components were necessary in order for the approach to be effective in this patient population. Although previous clinical trials have looked at the combination of an EGFR inhibitor and a MET inhibitor have been done in the lung cancer space, they were not conducted in a biomarker-selected population, says Sequist. 

Therefore, TATTON was the first clinical trial to use the combination of 2 agents in a population that has that biomarker signature. In a cohort of 46 patients who had previously received either a first- or second-generation EGFR TKI, treatment with the combination led to an objective response rate of 52%, with 24 partial responses. The median duration of response was 7.1 months. These findings were particularly exciting, says Sequist, as they show that the concept of pairing these 2 agents can be effective when they are given to selected patients.

Lecia V. Sequist, MD, MPH, thoracic medical oncologist and director of the Center for Innovation in Early Cancer Detection at Massachusetts General Hospital Cancer Center, discusses the rationale for the TATTON trial in non–small cell lung cancer (NSCLC).

Lecia V. Sequist, MD, MPH

Articles

Dr. Sequist on Pembrolizumab Monotherapy in Nonsquamous NSCLC

Dr. Sequist on Implications of the IMpower150 Trial in Advanced Nonsquamous NSCLC

Dr. Sequist on Rationale for TATTON Trial in EGFR-Mutant Lung Cancer