Sean Bohen, MD, PhD
Durvalumab (Imfinzi) significantly improved progression-free survival (PFS) when used as a sequential treatment in patients with locally-advanced, unresectable non–small cell lung cancer (NSCLC) who had not progressed following standard care with platinum-based chemotherapy and radiotherapy, meeting the primary endpoint of the phase III PACIFIC trial.
AstraZeneca, the manufacturer of the PD-L1 inhibitor, intends to present these initial findings from the PACIFIC trial at an upcoming medical meeting. The company has also initiated talks with regulatory authorities regarding approval for durvalumab for use in this setting.
“These are highly encouraging results for patients with locally-advanced lung cancer for whom surgery is not an option. We look forward to working with regulatory authorities around the world to bring Imfinzi to lung cancer patients as soon as possible. Alongside this, we continue to explore Imfinzi’s full potential as monotherapy as well as in combination with tremelimumab and other medicines in areas of continued unmet need across multiple types of cancer,” Sean Bohen, MD, PhD, executive vice president, global medicines development, and chief medical officer at AstraZeneca, said in a statement.
The double-blind PACIFIC trial took place at 235 centers in 26 countries and included an “all-comer” patient population who had locally-advanced, unresectable (stage III) NSCLC with no disease progression after concurrent therapy with platinum-based chemotherapy and radiation. Patients were randomized in a 2:1 ratio to durvalumab or placebo. PFS was the primary endpoint, along with overall survival (OS).
An independent data monitoring panel determined at an interim analysis that the study had met the primary PFS endpoint. The benefit/risk profile was also shown to favor the durvalumab arm. OS continues to be evaluated.
Results from the phase II ATLANTIC trial presented late last year at the 17th World Lung Cancer Conference showed that durvalumab demonstrated a clinical benefit in the second-line setting and beyond in heavily pretreated patients with locally advanced or metastatic NSCLC.
In the study, the level of response increased with higher levels of PD-L1 expression. The highest overall response rate (ORR) of 30.9% (95% CI, 20.2-43.3) occurred in patients with PD-L1 expression on ≥90% of tumor cells. ORR was 16.4% (95% CI, 10.8-23.5) in patients with PD-L1 expression ≥25%, and 7.5% (95% CI, 3.1-14.5) in patients with PD-L1 expression levels of <25%.
The 1-year OS rates were 48% and 51% in patients with PD-L1 levels of ≥25% and ≥90%, respectively. The median OS was 9.3 months, 20.9 months, and not yet reached in the <25%, ≥25%, and ≥90% PD-L1 expression groups, respectively. In the 3 cohorts, the median PFS was 1.9, 3.3, and 2.4 months, respectively.
Most adverse events (AEs) were low grade and resolved with treatment delay and/or immunosuppressive interventions. Treatment-related AEs leading to discontinuation occurred in 2.7% of patients.
The phase III MYSTIC and PEARL trials are examining single-agent durvalumab in the frontline setting for NSCLC. Additionally, durvalumab is also being explored in combination with the CTLA-4 inhibitor tremelimumab as part of the phase III MYSTIC, NEPTUNE, and POSEIDON trials.
Earlier this month, the FDA granted an accelerated approval to durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
The approval was based on the single-arm phase I/II Study 1108, which included 182 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression following platinum-containing chemotherapy.
In the study, the ORR per blinded independent central review was 17.0% (95% CI, 11.9-23.3). At the data cutoff, the median duration of response was not reached (range, 0.9+ to 19.9+ months).
Among 95 patients with high PD-L1 expression, the ORR was 26.3% (95% CI, 17.8-36.4). In the cohort of 73 patients with low or no PD-L1 expression, the ORR was 4.1% (95% CI, 0.9-11.5).