The immune checkpoint inhibitor durvalumab may have a role in the treatment of EGFR+ tumours with high PD-L1 expression, results from the phase 2 ATLANTIC study show.
Published this week in Lancet Oncology the open-label, single-arm trial involved 444 patients with heavily pre-treated advanced non-small cell lung cancer (NSCLC) from 139 study centres in Asia, Europe, and North America.
The researchers led by Marina Chiara Garassino from the National Cancer Institute in Milan, Italy, enrolled patients into three cohorts according to their EGFR/ALK status and tumour cell expression of PD-L1. Those in cohort 1 (n=111) had EGFR+/ALK+ NSCLC with at least 25%, or less than 25%, of tumour cells with PD-L1 expression.
Patients in cohorts 2 (n=265) and 3 (n=68) had EGFR−/ALK− NSCLC; cohort 2 included patients with at least 25%, or less than 25%, of tumour cells with PD-L1 expression, and cohort 3 included patients with at least 90% of tumour cells with PD-L1 expression.
Study participants received durvalumab (10 mg/kg) every 2 weeks, via intravenous infusion, for up to 12 months.
The authors observed “durable responses and encouraging overall survival data” across all cohorts, with a higher proportion of patients with EGFR−/ALK− tumours achieving a response versus patients with EGFR+/ALK+ tumours.
For example, among patients with at least 25% of tumour cells expressing PD-L1 who were evaluable for objective response per independent central review, an objective response was achieved in 9 (12·2%, 95% CI 5·7–21·8) of 74 patients in cohort 1 and 24 (16·4%, 10·8–23·5) of 146 patients in cohort 2. In cohort 3, 21 (30·9%, 20·2–43·3) of 68 patients achieved an objective response.
The safety profile and activity of durvalumab was largely consistent with other PD-1 and PD-L1 inhibitors in pretreated patients with EGFR–/ALK– NSCLC, the study authors noted.
“Our results…suggest durvalumab might have a role in the treatment of EGFR+ tumours with high PD-L1 expression. Additional prospectively designed controlled studies in patients with EGFR+/ALK+ NSCLC are warranted to further understand the activity of immune checkpoint inhibitors in this population,” the study authors concluded.
According to an accompanying editorial, the most notable contribution of ATLANTIC was that it represented the first prospective evaluation of an immune checkpoint inhibitor in a dedicated cohort of patients with EGFR+/ALK+ NSCLC.
Nonetheless, EGFR or ALK inhibitors followed by chemotherapy remained cornerstones of therapy for these patients, the editorialists said.
“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”.
For now, they advised clinicians to 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,” they added.