TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.
All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.
The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.
The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.
“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”
The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.
“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.
Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.
“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.
Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.
The primary end-point of the study is 24-month progression-free survival.
CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.
The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.
“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.
Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”
Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.
SOURCE: Provencio, Mario et al., WCLC 2018 .