medwireNews: The addition of ipilimumab to nivolumab does not improve the survival outcomes of patients with advanced squamous non-small-cell cancer (NSCLC) who have previously received chemotherapy, shows the phase 3 LUNG-MAP S1400I trial.
“Although nivolumab combined with ipilimumab has demonstrated superior efficacy to nivolumab alone in advanced melanoma and to first-line platinum-based chemotherapy in advanced NSCLC, the combination did not improve OS [overall survival] over nivolumab alone in patients with immunotherapy-naïve, pretreated advanced [squamous] NSCLC,” say Scott Gettinger (Yale Cancer Center, New Haven, Connecticut, USA) and fellow researchers.
After a median follow-up of 29.5 months, the median OS was 10 months among the 125 patients who were randomly assigned to receive nivolumab 3 mg/kg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks. This was comparable to the median OS of 11 months among the 127 patients who instead received nivolumab alone.
There were also no significant between-group differences in median investigator-assessed progression-free survival (3.8 vs 2.9 months) and objective response rate (18 vs 17%), reports the team in JAMA Oncology.
Median duration of response did, however, favor the combination arm, at 28.4 versus 9.7 months in the monotherapy arm, although the exclusion of six unconfirmed partial responses improved the median in the latter group to 13.2 months.
Gettinger and colleagues note that “[a]dditional biomarker analyses from this trial, including tumor PD-L1 expression and tumor sequencing, did not identify individual tumor characteristics predictive of benefit from either treatment over the other.”
However, a post-hoc exploratory analysis revealed that in the subgroup of patients with no PD-L1 expression (<1%), OS was better with the combination than nivolumab alone among those with a high tumor mutational burden (TMB; ≥10 mutations/Mb), whereas the combination appeared to be detrimental for patients with a TMB below the cutoff.
But the team cautions that “the exploratory nature of these combined analyses and the small number of patients in each subset limit conclusions.”
Treatment-related adverse events of grade 3 or higher were observed in 39.5% of patients given nivolumab plus ipilimumab and 33.3% of those given nivolumab alone. Fatigue and pneumonitis were the most common events of this grade in both groups, occurring at rates of 8.9% versus 5.7% and 7.3% versus 4.9%, respectively.
Moreover, 66% of patients given the combination had an immune-related adverse event of any grade as did 59% of patients given monotherapy.
The rate of treatment discontinuation due to toxicity was 25% in the combination group and 15% in the monotherapy group, with respective treatment-related mortality rates of 2.4% and 0.8%.
The researchers point out that at least two ongoing studies are investigating the role of nivolumab plus ipilimumab as salvage therapy in patients with acquired or primary resistance to PD-L1 axis inhibitor therapy.
“Until these studies and others are completed, there will continue to be no role for combination therapy with nivolumab and ipilimumab in patients with pretreated advanced NSCLC,” they conclude.
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