Durvalumab activity demonstrated in advanced NSCLC
medwireNews: Heavily pretreated patients with advanced non-small-cell lung cancer (NSCLC) have a durable response to treatment with the anti-programmed cell death ligand 1 (PD-L1) monoclonal antibody durvalumab, show results from the phase II ATLANTIC study.
“[T]he proportion of patients achieving a response were higher in patients whose tumours expressed higher levels of PD-L1, but responses were durable irrespective of PD-L1 expression status,” Marina Garassino (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) and colleagues remark.
They add: “Our findings confirm preliminary results from a previous phase 1–2 study of durvalumab in patients with advanced NSCLC, and show that the clinical activity and safety profile of durvalumab is consistent with other anti-PD-1 and anti-PD-L1 agents.”
The ATLANTIC study, conducted across 139 study centers in Asia, Europe, and North America, involved three cohorts of patients with NSCLC defined by EGFR/ALK status and tumor expression of PD-L1, who received intravenous durvalumab 10 mg/kg every 2 weeks, for up to 12 months.
Patients in cohort 1 (n=111) had NSCLC positive for alterations in EGFR and ALK with increased tumor PD-L1 expression defined as 25% or higher. The same cutoff was used for patients in cohort 2 (n=265), who all had EGFR- and ALK-negative disease, while cohort 3 included 68 patients with EGFR- and ALK-negative NSCLC with at least 90% of tumor cells expressing PD-L1. All patients had received at least two previous treatment regimens.
The researchers report in The Lancet Oncology that the objective response rate among patients with at least 25% of tumor cells expressing PD-L1 was 12.2% of 74 evaluable patients in cohort 1 and 16.4% of 146 in cohort 2, with median follow-up durations of 6.7 and 9.2 months, respectively.
In cohort 3, 30.9% of patients achieved an objective response during a median follow-up period of 7.0 months.
However, Garassino et al point out that the objective response rate was 15.7% in a subset of 70 patients in cohort 2 who had at least 90% of tumor cells expressing PD-L1.
“Thus, the higher proportion of patients who achieved an objective response in cohort 3 might be due to a factor other than the increased PD-L1 expression; for example, patients in cohort 3 were less heavily pretreated than those in cohort 2,” they write.
Median overall survival was longer for patients with at least 25% of tumor cells with PD-L1 expression (11–13 months) versus those with less than 25% (9–10 months), regardless of EGFR/ALK status. Median overall survival had not been reached in cohort 3, but the overall survival at 1 year was 51%.
The investigators also report that durvalumab “had an acceptable tolerability profile.”
The most common grade 3 or 4 treatment-related adverse events were pneumonitis (n=4), elevated gamma-glutamyltransferase (n=4), diarrhea (n=3), and infusion-related reactions (n=3), and any immune-mediated events were manageable with standard treatment guidelines.
Garassino and co-authors conclude: “The ATLANTIC study makes an important contribution to the body of evidence on the efficacy of immune checkpoint inhibitors in NSCLC.”
They add: “Although clinical applications of these data might be few, one potentially interesting question is whether durvalumab has a role in the treatment of EGFR+ tumours with high PD-L1 expression, and could be the subject of further clinical investigation.”
In an accompanying comment, Jessica Lin and Justin Gainor, both from Massachusetts General Hospital Cancer Center, in Boston, USA, write: “Although immune checkpoint inhibitor monotherapy might ultimately have a role in highly select patients with oncogene-driven tumours, additional studies are needed to better define these patients.”
Indeed they point out that although patients with ALK-positive and EGFR-positive NSCLC were grouped together in cohort 1, “patients with ALK+ NSCLC had a higher frequency of PD-L1 overexpression than patients with EGFR+ NSCLC, yet the activity of durvalumab was concentrated solely in the EGFR+ group.”
Lin and Gainor conclude: “For now, clinicians should consider directing patients with EGFR+/ALK+ NSCLC to clinical trials evaluating immunotherapy combinations. Such efforts might create a potential space for immune-based treatment approaches in these molecular subgroups—thus far a largely uncharted territory.”
By Laura Cowen
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