NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further
The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.
Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.
“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.
The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.
Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”
“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”
Importance of Neoadjuvant Immunotherapy
New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.
Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).
In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).
Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.
“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
Neoadjuvant slow to catch on
About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.
Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.
The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.
In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.
In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.
“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”
Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.
“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.