Objective response rate was higher in patients whose tumors were PD-L1–high (≥ 25% tumor cells). However, the benefit spans all subgroups, and it is independent of the line of treatment.— Marina Garassino, MD
Tweet this quote
Durvalumab was active and led to long-lasting response in a cohort of heavily pretreated patients with epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) wild-type locally advanced and metastatic non–small cell lung cancer (NSCLC), particularly among patients whose tumors exceeded the 25% programmed cell death ligand 1 (PD-L1) cutoff, according to the results of the phase II ATLANTIC trial. Marina Garassino, MD, of the Medical Oncology Division of the National Cancer Institute in Milan, Italy, presented these findings at 2016 World Conference on Lung Cancer in Vienna.1
Durvalumab is a selective, high-affinity monoclonal antibody that blocks PD-L1 from binding to the programmed cell death protein 1 (PD-1). Treatment with anti–PD-1/PD-L1 antibodies has demonstrated a significant benefit among patients with advanced NSCLC, but disease progression after two lines of chemotherapy often leaves these poor-prognosis patients with a lack of standard treatment options.
ATLANTIC is an open-label, single-arm trial including patients with stage IIIB/IV NSCLC who received at least two prior systemic treatment regimens, one platinum-based. The study initially enrolled all-comers but was later restricted to patients with high expression of
PD-L1 (at least 25% of tumor cells with membrane staining), noted Dr. Garassino.
The study included three independent cohorts, but the data presented by Dr. Garassino at the World Conference on Lung Cancer focused on the results from the 265 patients in cohort 2 (divided into PD-L1–low/negative [< 25% tumor cells] and PD-L1–high [≥ 25% tumor cells]) and 68 patients in cohort 3 (PD-L1–high [≥ 90% tumor cells]).
Patients were treated with intravenous durvalumab at 10 mg/kg every 2 weeks for up to 12 months. A total of 60% of patients in cohort 2 and 40% of patients in cohort 3 received durvalumab as fourth-line therapy or beyond. The primary endpoint of the study was overall response rate.
Baseline characteristics were similar in the two cohorts. The mean number of prior regimens in cohort 2 was 3.2 (20.8% with squamous histology), compared with 2.6 regimens in cohort 3 (29.4% with squamous histology).
“Objective response rate was higher in patients whose tumors were PD-L1–high (≥ 25% tumor cells),” reported Dr. Garassino. “However, the benefit spans all subgroups, and it is independent of the line of treatment. Of note, it is also present for patients with central nervous system metastases.”
Investigators observed a response rate of 30.9% in cohort 3; in cohort 2, the rate was 16.4% in the PD-L1–high patients (n = 146) and 7.5% in patients from the PD-L1–low segment (n = 93). Responses to durvalumab appeared durable, with 1-year overall survival rates of 50.8% in cohort 3 and 47.7% and 34.5% in cohort 2, PD-L1–high and PD-L1–low, respectively.
Median follow-up for overall survival was 9.4 months (PD-L1 ≥ 25%), 9.3 months (PD-L1 < 25%), and 7.0 months (PD-L1 ≥ 90%). “I would like to reiterate that these patients were highly pretreated,” Dr. Garassino added. Median progression-free survival was 2.4 months in cohort 3 and 3.3 months and 1.9 months in cohort 2 for PD-L1–high and –low, respectively.
Durvalumab showed a manageable safety and tolerability profile; most adverse events were low grade and resolved with treatment delay and/or immunosuppressive interventions. Grade ≥ 3 treatment-related adverse events occurred in 8.3% of patients in cohort 2 and 17.6% of patients in cohort 3. However, treatment-related adverse events leading to treatment discontinuation were noted in 3% of cohort 2 patients and 1.5% of cohort 3 patients, revealed Dr. Garassino.
These results are consistent with other anti–PD-1/PD-L1 therapies in metastatic NSCLC, but ongoing phase III studies will clarify the role of durvalumab (alone or in combination therapy) in NSCLC, she added. ■
Disclosure: Dr. Garassino has affiliations with AstraZeneca, Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Boehringer Ingelheim, and Eli Lilly. The trial was supported by AstraZeneca.
1. Garassino MC, Vansteenkiste JF, Kim J, et al: Durvalumab in ≥ 3rd-line locally advanced or metastatic, EGFR/ALK wild-type NSCLC. 2016 World Conference on Lung Cancer. Abstract PL04a.03. Presented December 7, 2016.
There was quite impressive survival in this third-line or more cohort of patients, with a median survival in the strongest PD-L1–expressing patients that is clearly going to exceed 1 year.— Michael Boyer, MBBS, PhD
Tweet this quote
“This drug [durvalumab] clearly...!-->!-->