Dr Awad on the FDA Approval of Perioperative Nivolumab for Resectable NSCLC

Mark Awad, MD, PhD, chief, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the significance of the FDA approval of perioperative nivolumab (Opdivo) for patients with resectable non–small cell lung cancer (NSCLC).

 in combination with platinum-doublet chemotherapy in the neoadjuvant setting, followed by nivolumab monotherapy in the adjuvant setting, for the treatment of adult patients with resectable NSCLC with no known 

 rearrangements. This regulatory decision was supported by data from the phase 3 CheckMate 77T trial (NCT04025879), in which the median event-free survival (EFS) in patients who received perioperative nivolumab was not reached (95% CI, 28.9 months-not evaluable) vs 18.4 months (95% CI, 13.6-28.1) in patients who received placebo plus chemotherapy (HR, 0.58; 95% CI, 0.43-0.78; 

Recent advancements in NSCLC management have demonstrated significant progress, particularly in early-stage disease, Awad begins. Historically, early-stage NSCLC posed a therapeutic challenge due to high recurrence rates following surgery, he says. For decades, the standard of care (SOC) for this patient population consisted of surgery followed by adjuvant chemotherapy, he notes. However, the introduction of immune checkpoint inhibitors has revolutionized this treatment paradigm, he emphasizes. These agents have initially been shown to be effective in the metastatic setting and are now under evaluation in perioperative settings for earlier-stage disease, Awad explains.

The CheckMate 77T trial, which evaluated the efficacy of perioperative immunotherapy plus chemotherapy, represents a pivotal study in this domain, he adds. This approach builds on those of previous trials that investigated immunotherapy solely in the adjuvant setting, as well as those that examined neoadjuvant immunotherapy alone or in combination with chemotherapy, he notes.

Awad states that CheckMate 77T and similar phase 3 trials, such as KEYNOTE-671 (NCT03425643) and AEGEAN (NCT03800134), demonstrated that the addition of immunotherapy to chemotherapy before surgery, followed by postoperative immunotherapy, significantly reduced recurrence rates in early-stage, resectable lung cancer. Emerging data indicate a clear EFS benefit with this approach, he says. These findings support the use of immunotherapy regimens to enhance SOC treatment for patients with early-stage lung cancer, potentially increasing cure rates and prolonging survival, he emphasizes. As ongoing trials yield long-term follow-up data, the role of immunotherapy in early-stage lung cancer is expected to solidify, paving the way for broader clinical application and improved patient prognosis, he concludes.

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Mark Awad, MD, PhD, discusses the significance of the FDA approval of perioperative nivolumab for patients with resectable NSCLC.

Mark M. Awad, MD, PhD, clinical director of the Thoracic Oncology Treatment Center and physician at Dana-Farber Cancer Institute, and an assistant professor of medicine at Harvard Medical School, discusses the main objectives of the phase 2 GEOMETRY mono-1 study in patients with 

ex14)-mutated non–small cell lung cancer (NSCLC).

The trial had several objectives, says Awad. Many mutations that can impact 

ex14 can be identified, and some of these mutations reside in the flanking introns, explains Awad. To this end, one of the main goals of the trial was to determine whether certain mutations correlated more with other co-mutations or genomic abnormalities, adds Awad. 

Additionally, investigators wanted to develop a better understanding of PD-L1 expression and tumor mutational burden in this molecular lung cancer subtype, says Awad.

By examining patients who had serial biopsies that underwent sequencing, investigators also set out to identify putative mechanisms of acquired resistance to MET kinase inhibitors, adds Awad. The hope is that a greater understanding of resistance mechanisms could inform the development of drugs that could potentially overcome or prevent resistance from emerging, concludes Awad.

Mark M. Awad, MD, PhD, discusses the main objectives of the phase 2 GEOMETRY mono-1 study in patients with MET exon 14 skipping (METex14)-mutated non–small cell lung cancer (NSCLC).

Dr. Awad on Objectives of the Phase 2 GEOMETRY Mono-1 Study in NSCLC

Mark M. Awad, MD, PhD, clinical director of the Thoracic Oncology Treatment Center and physician at Dana-Farber Cancer Institute, and an assistant professor of medicine at Harvard Medical School, discusses acquired resistance to MET inhibitors in 

ex14)–mutated non–small cell lung cancer (NSCLC).

ex14-mutant NSCLC are varied and can be complex, says Awad.

Some patients develop on-target acquired resistance mutations, wherein 

 mutates a second time, leading to secondary mutations within the MET kinase domain. This is particularly common in certain recurring positions, such as D1228, Y1230, L1195, and others. Additionally, a subset of patients can develop acquired amplification of the 

A number of off-target resistance mechanisms or bypass track activations can also manifest, such as amplification of wild-type 

 or other MAP kinase pathway molecules, says Awad. This increases the complexity of resistance mechanisms in this subtype of lung cancer. The ultimate goal is to develop improved therapies that prevent resistance from emerging, concludes Awad.

Mark M. Awad, MD, PhD, discusses acquired resistance to MET inhibitors in MET exon 14 skipping (METex14)–mutated non–small cell lung cancer (NSCLC).

Mark M. Awad, MD, PhD

Articles

Dr Awad on the FDA Approval of Perioperative Nivolumab for Resectable NSCLC

Dr. Awad on Objectives of the Phase 2 GEOMETRY Mono-1 Study in NSCLC

Dr. Awad on Acquired Resistance to MET Inhibitors in NSCLC