Tina Cascone, MD, PhD, of the University of Texas MD Anderson Cancer Center, discusses the impact of the CheckMate 77T study on the treatment approach for non–small cell lung cancer (NSCLC).
Tina Cascone, MD, PhD, from the Division of Cancer Medicine, Department of Thoracic-Head & Neck Med Onc, University of Texas MD Anderson Cancer Center, discusses the impact of the CheckMate 77T study (NCT04025879) on the treatment approach for non–small cell lung cancer.
Can you give us an overview of how neoadjuvant immunotherapy fits into current treatment approach for non–small cell lung cancer?
For patients with resectable and non–small cell lung cancer, surgery still remains the primary curative treatment approach. However, if treated with surgery alone, 35% to 60% of these patients, unfortunately, will experience disease relapse. And we know historically that platinum-based chemotherapy, given via neoadjuvant or adjuvant therapy, only provides a 5% improvement in 5-year overall survival.
Immunotherapy has revolutionized the treatment landscape for non–small cell lung cancer in the metastatic advanced setting, in the locally advanced and resectable setting. It has been brought into the early stage setting with the hope of triggering an effective immune response early on when the tumor is still in place with theoretically the highest antigen load and minimal clonal resistance when the immune system is also intact, with the hope to trigger memory for an improvement in long-term outcomes for our patients with resectable non–small cell lung cancer.
Neoadjuvant nivolumab plus chemotherapy is now the standard of care, and neoadjuvant treatments for eligible patients with resectable non–small cell lung cancer have demonstrated statistically significant and clinically meaningful improvements in the event-free survival and in the rate of pathological complete response as compared to platinum-based chemotherapy alone in the CheckMate 816 study.
How do you see the results of CheckMate 77T impacting treatment approaches for non–small cell long cancer moving forward?
The CheckMate 77T met its primary end point with neoadjuvant and nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab, demonstrating a statistically significant and clinically meaningful EFS [event-free survival] improvement as compared to neoadjuvant chemotherapy placebo followed by surgery and adjuvant placebo in our patients with resectable non–small cell lung cancer. The EFS benefit was seen across most key subgroups. PCR [pathologic complete response] and MPR [major pathological response] rates were also improved. And in exploratory analysis, we learned that perioperative nivolumab favored EFS in patients with a PCR with a trend toward improved EFS in patients with our PCR. Among patients eligible for adjuvant therapy, preoperative nivolumab improved EFS vs chemotherapy regardless of PCR status. Neoadjuvant nivolumab plus chemotherapy continued to provide benefit over chemotherapy in patients who were not able to receive adjuvant therapy.
So the CheckMate 77T is the first phase 3 perioperative study that builds on the current standard of care, neoadjuvant nivolumab plus chemo, and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer. The safety signals were in alignment with what we have learned with prior perioperative studies and the surgical feasibility was similar between treatment arms.
And so I think moving forward, our next step will focus on identifying patient and disease characteristics that will tell us who are the individuals that can benefit from a neoadjuvant chemo-immunotherapy approach alone, and who are the patients who instead require more intensified adjuvant treatments, including the strategy that was tested in the perioperative CheckMate 77T study or a switch agent, a type of adjuvant regimen where we can intensify therapy in the adjuvant treatment for patients who have not achieved a response nor benefited from a neoadjuvant chemo-immunotherapy approach. A lot of research and rationale studies to perform going forward to help our patients to improve their outcomes and hopefully cure early-stage lung cancer.