Nivolumab benefit for NSCLC persists at 5-year follow-up

BARCELONA – Nivolumab, compared with docetaxel chemotherapy, led to a fivefold improvement in 5-year overall survival among previously treated patients with non–small cell lung cancer (NSCLC), according to a pooled analysis of data from the phase 3 CheckMate 017 and 057 trials.

^{Sharon Worcester/MDedge News}

Dr. Scott Gettinger

The 5-year overall survival (OS) rates from the two randomized registrational trials, which established the programmed death-1 (PD-1) inhibitor nivolumab as the standard salvage therapy for NSCLC, were 13.4% vs. 2.6% (median, 11.1 vs. 8.1 months) with nivolumab and docetaxel, respectively, Scott Gettinger, MD, reported at the World Conference on Lung Cancer.

“These are the first randomized trials to report 5-year outcomes for a PD-1 axis inhibitor in patients with previously treated advanced non–small lung cancer,” said Dr. Gettinger, a professor at the Yale Comprehensive Cancer Center, New Haven, Conn. “This is really unprecedented; we wouldn’t expect many patients to be out 5 years in this scenario.”

Notably, the 5-year OS benefit was seen in both trials, he said, explaining that each compared nivolumab and docetaxel, but CheckMate 017 included patients with only squamous NSCLC, and CheckMate 057 included only non–squamous NSCLC patients.

The trials randomized 272 and 582 patients, respectively, and both demonstrated significantly improved 12-month OS with nivolumab – regardless of programmed death-ligand 1 (PD-L1) expression levels. Common eligibility criteria included stage IIIb/IV disease, good performance status (ECOG performance score of 0-1), and 1 prior platinum-based chemotherapy; CheckMate 057 further allowed prior tyrosine kinase inhibitor treatment for known anaplastic lymphoma kinase (ALK) translocation or epidermal growth factor receptor (EGFR) mutation, and allowed prior maintenance therapy. Doses in both trials were 3 mg/kg of nivolumab every 2 weeks or 75 mg/m² of intravenous docetaxel every 3 weeks until disease progression or unacceptable toxicity.

The pooled data also showed an improvement in progression-free survival (PFS) at 5 years (8% vs. 0%) with nivolumab vs. docetaxel groups.

“Again, we don’t see this in trials – more commonly we see zero patients without progression, and that’s what we saw with the docetaxel arm,” said Dr. Gettinger, who also is the Disease Aligned Research Team Leader, Thoracic Oncology Program, at the cancer center.

The median duration of responses with nivolumab was 19.9 months vs. 5.6 months with docetaxel, and 32.2% of nivolumab responders were still without progression at 5 years, he noted.

A common question in the clinic relates to the prognosis in patients who do well with PD-1 axis inhibitors, which prompted an additional analysis across the two trials, he said, noting that 60%, 78%, and 88% of patients who had not progressed at 2, 3, or 4 years, respectively, also had not progressed at 5 years, and 80%, 93%, and 100%, of patients in those groups were alive at 5 years. In the docetaxel arm, only 4, 1, and 0 patients had PFS at 2, 3, and 4, years, respectively, and none of those patients survived to 5 years, he said.

No new safety signals were seen with long-term follow-up, he added.

“In fact there was only one grade 3 or higher toxicity that was related to treatment in the nivolumab arm, and this was a grade 3 lipase elevation. There was one patient who discontinued nivolumab after 3 years, and this was for a grade 2 rash and eczema that had waxed and waned since starting nivolumab,” he said.

Also of note, 10% of nivolumab-treated patients who were off treatment at 5 years – for variable periods of time – had not progressed and had not received subsequent therapy.

“So we clearly see benefit in our patients long after they finish a course or stop for some reason,” he said.

CheckMate 017 and 057 were funded by Bristol-Myers Squibb. Dr. Gettinger reported advisory board and/or consulting work for, and/or research funding from Bristol-Myers Squibb, Nektar Therapeutics, Genentech/Roche, Iovance, and Takeda/Ariad.

SOURCE: Gettinger S et al. WCLC 2019, Abstract PR04.03.