Fears of delaying surgery
In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.
“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”
In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
CheckMate 816 details
In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.
After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.
At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.
Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.
In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.
The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.
The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.
Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.
CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.
A version of this article first appeared on Medscape.com.