Nivolumab–ipilimumab an option for untreated, advanced NSCLC regardless of PD-L1 levels
medwireNews: Individuals with advanced non-small-cell lung cancer (NSCLC) derive an overall survival (OS) benefit from first-line treatment with nivolumab plus ipilimumab irrespective of PD-L1 expression, report the CheckMate 227 investigators.
“This result is consistent with previous reports involving patients with melanoma and renal-cell carcinoma,” they write in The New England Journal of Medicine.
The findings were simultaneously reported at the ESMO Congress 2019 – held in Barcelona, Spain – by Solange Peters (Lausanne University Hospital, Switzerland) who commented that “this dual immunotherapy represents a potential new first-line option for patients with advanced NSCLC.”
The phase III trial enrolled individuals with stage IV or recurrent disease and randomly assigned those with PD-L1 levels of at least 1% to receive either nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (n=396), nivolumab 240 mg every 2 weeks (n=396), or up to four cycles of platinum-based doublet chemotherapy every 3 weeks (n=397). Participants with PD-L1 expression below 1% received either the dual immunotherapeutic regimen at the same dose (n=187) or chemotherapy, either with nivolumab 360 mg every 3 weeks (n=177) or alone (n=186).
The investigators previously reported data for one of the co-primary endpoints – progression-free survival with nivolumab plus ipilimumab versus chemotherapy in patients with high tumor mutational burden (≥10 mutations/Mb) – and now, they report on the other primary endpoint of OS for the same comparison but in the PD-L1-positive population.
The dual immunotherapy achieved a median OS of 17.1 months, which was longer than the 14.9 months observed with chemotherapy, and equated to a significant hazard ratio (HR) for death of 0.79, albeit without the proportional hazards assumption being met. The study authors note, however, that the HR “provides an overall estimate of benefit and should be interpreted in the context of the shape of the curves, which are characterized by transient initial survival benefit with chemotherapy, followed by long-term benefit with nivolumab plus ipilimumab.”
In line with this, the 1-year OS rate was 62.6% for the immunotherapy group and 56.2% for the chemotherapy group, with corresponding 2-year OS rates of 40.0% and 32.8%.
The objective response rates were not dissimilar for the combination immunotherapy and chemotherapy regimens, at 35.9% and 30.0%, respectively, but the median duration of response was much longer with nivolumab plus ipilimumab, at 23.2 versus 6.2 months.
A prespecified exploratory analysis of the cohort with PD-L1 levels below 1% again showed better median OS with nivolumab–ipilimumab than chemotherapy, at 17.2 and 12.2 months, respectively, and a significant HR for death of 0.62, with 40.4% and 23.0% of participants alive at the 2-year mark.
In light of these results, Peters noted that the audience would not be surprised to find out that the OS benefit associated with the dual immunotherapy was maintained in the overall trial population, at a median of 17.1 months versus 13.9 months with chemotherapy (HR=0.73).
The incidence of grade 3 or 4 adverse events (AEs) attributable to treatment was comparable in the immunotherapy and chemotherapy arms (32.8 vs 36.0%), but serious AEs were more frequent with immunotherapy (24.5 vs 13.9%), as were discontinuations due to AEs (18.1 vs 9.1%).
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