Durvalumab in Heavily Pretreated EGFR/ALK Wildtype Advanced NSCLC

Results from the ATLANTIC study
07 Dec 2016

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. 

Reference

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. 

Last update: 07 Dec 2016

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