medwireNews: The PD-L1 inhibitor durvalumab, either given alone or alongside the CTLA-4 inhibitor tremelimumab, has clinical activity in the third- or later-line treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), indicate ARCTIC trial results.
As reported in the Annals of Oncology, the two-cohort phase 3 trial recruited 595 individuals who had already received platinum-based doublet chemotherapy and at least one other systemic regimen, but not prior immunotherapy with agents targeting PD-1, PD-L1, or CTLA-4, for stage III–IVB disease that was negative for EGFR or ALK alterations.
The participants of one cohort, all of whom had tumor cell PD-L1 levels of at least 25%, were randomly assigned to receive durvalumab 10 mg/kg every 2 weeks for up to a year or investigator’s choice of one of three standard of care (SOC) therapies, namely, erlotinib, gemcitabine, or vinorelbine. For the second cohort, which comprised those with PD-L1 levels below 25%, the treatment options were:
- durvalumab 20 mg/kg plus tremelimumab 1 mg/kg every 4 weeks for up to 12 weeks, followed by durvalumab 10 mg/kg every 2 weeks for 34 weeks;
- durvalumab at the single-agent dose as outlined above for up to 1 year;
- tremelimumab 10 mg/kg every 4 weeks for 24 weeks, then every 12 weeks for 24 weeks; or
- investigator’s choice of SOC.
In the first cohort (n=126), durvalumab monotherapy was associated with better overall survival (OS) and progression-free survival (PFS) than the SOC. Specifically, the median OS and PFS durations were 11.7 versus 6.8 months and 3.8 versus 2.2 months, giving a hazard ratio (HR) for death of 0.63 and for progression or death of 0.71.
Other outcomes – such as the objective response rate and duration of response – also favored durvalumab, but the investigators stress that this cohort was not powered for statistical comparisons.
They highlight, however, that these findings are consistent with those from a cohort of similar patients from the phase 2 ATLANTIC trial of single-agent durvalumab.
In the second cohort (n=469), treatment with the combination of durvalumab and tremelimumab resulted in a longer median OS than SOC treatment, at 11.5 and 8.7 months, respectively, and an HR for death of 0.80, but the difference was not statistically significant.
Median PFS was identical in both groups, at 3.5 months, but the HR for progression or death of 0.77 favored the experimental treatment, although again this did not reach statistical significance.
The OS and PFS HRs for the comparison of durvalumab monotherapy with SOC in this cohort also favored the PD-L1 inhibitor, but again without statistical significance. However, the comparisons of single-agent tremelimumab with SOC appeared to favor SOC for both OS and PFS.
David Planchard (Institut Gustave-Roussy, Villejuif, France) and team note that one of the key limitations of the trial was the challenging recruitment for both cohorts, which arose “from the changing treatment landscape (including approval of anti-PD-1/PD-L1 treatments across treatment lines and extensive clinical trial programs) that made it difficult to recruit immunotherapy-naïve patients in the [third- or later-line] setting.”
Nonetheless, they conclude: “Given the poor prognosis for heavily pretreated patients with [metastatic] NSCLC and limited data in the [third- or later-line] setting, these results expand the body of evidence for advanced treatment lines and the predictive role of tumor PD-L1 expression in patients with [metastatic] NSCLC.”
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