In the phase II ATLANTIC study, durvalumab was active and led to durable responses in heavily pretreated patients with EGFR/ALK wildtype locally-advanced and metastatic non-small-cell lung cancer (NSCLC). The activity was numerically greater for patients whose tumours exceeded the 25% PD-L1 cut-off. The results were presented at a Plenary session entitled Immune Checkpoint Inhibitors in Advanced NSCLC at the World Conference on Lung Cancer (5-8 December 2016, Vienna, Austria).
Patients with NSCLC who progress after two lines of chemotherapy have few treatment options and poor outcomes. Durvalumab is an antibody targeting programmed cell death ligand-1 (PD-L1).
ATLANTIC is an open-label, single-arm trial in patients with stage IIIB–IV NSCLC with WHO performance status 0 or 1, who received at least two prior systemic treatment regimens, including one platinum-based.
The study initially enrolled all-comers and then was restricted to patients with PD-L1 high tumours (at least 25% of tumour cells with membrane staining).
The study includes three cohorts; however, the researchers reported at the meeting the final results in cohorts 2 and 3 that had EGFR/ALK wildtype or unknown status. Patients enrolled in cohort 3 had at least 90% of tumour cells with PD-L1 staining.
The primary endpoint was overall response rate (ORR) according to RECIST v1.1, based on independent central review. Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
As of 3 June 2016, 265 patients were included in cohort 2 and 68 in cohort 3. Responses were durable; in cohort 2, patients with PD-L1 ≥25%, the ORR was similar in patients with squamous and non-squamous histology.
The DCR was 28.8% in cohort 2 of patients with high PD-L1 and 20.4% in patients with low/negative PD-L1. The DCR was 38.2% in cohort 3.
The median PFS was 3.3 month in cohort 2 of patients with high PD-L1, 1.9 month in same cohort but in patients with low/negative PD-L1. It was 2.4 month in cohort 3.
One-year OS rate was 47.7% in cohort 2 of patients with high PD-L1, 34.5% in same cohort but in patients with low/negative PD-L1, and 50.8% in cohort 3.
Most adverse events were low grade and resolved with treatment delay and/or immunosuppressive interventions. Overall, 10.2% of patients had at least grade 3 treatment-related adverse events and 2.7% had treatment-related adverse events leading to discontinuation.
The authors concluded that the results are consistent with other anti-PD-1/PD-L1 therapies in metastatic, relapsed NSCLC and support further development of durvalumab.
PL04a.03 – Garassino MC, Vansteenkiste JF, Kim J, et al. Durvalumab in ≥3rd-Line Locally Advanced or Metastatic, EGFR/ALK Wild-Type NSCLC: Results from the Phase 2 ATLANTIC Study. Presented at World Conference on Lung Cancer, 5-8 December 2016, Vienna, Austria.