In a phase 3 trial, concurrently administered durvalumab and platinum-based chemoradiotherapy did not increase progression-free survival in stage III unresectable non–small cell lung cancer.
The phase 3 PACIFIC-2 trial (NCT0351997) of concurrent durvalumab (Imfinzi) and chemoradiotherapy (CRT) did not meet its primary end point of progression-free survival (PFS) compared with CRT alone in the treatment of unresectable, stage III non–small cell lung cancer (NSCLC), according to AstraZeneca, durvalumab’s manufacturer.1
“While the PACIFIC-2 trial results did not show what we hoped, the PACIFIC regimen remains the standard of care for patients with unresectable, stage III non-small cell lung cancer. As a community, we will take insights from these results to advance future research,” said Jeffrey D. Bradley, MD, vice chair of Proton Therapy and Technology Development, Penn Medicine, and principal investigator of PACIFIC-2, in a press release.1
Durvalumab administered after platinum-based CRT is the standard-of-care for unresectable, stage III NSCLC, and its use was supported with findings from the PACIFIC trial (NCT02125461). The PACIFIC-2 trial had the aim of addressing patients who progressed during CRT and were ineligible for subsequent durvalumab.
According to an initial safety and tolerability analysis of durvalumab plus CRT in this patient population, the profiles of the combination were broadly consistent with the known profiles of these treatments alone. However, an increased rate of infection was seen in the experimental arm during the concurrent treatment period.
“Our goal with the PACIFIC-2 trial was to address a remaining unmet need for patients in this setting by introducing immunotherapy even earlier and concurrently administering [durvalumab] with chemoradiotherapy. While today’s results did not reach statistical significance, we will learn from this trial and we remain committed to improving patient outcomes by expanding the benefit of immunotherapy to lung cancer patients across treatment settings,” said Susan Galbraith, executive vice president of oncology research and development, AstraZeneca, in a press release.1
PACIFIC-2 is a randomized, double-blind, placebo-controlled, multicenter, international phase 3 study assessing the safety and efficacy of concurrent durvalumab and CRT in patients with locally advanced, unresectable NSCLC. Patients were randomized 2:1.1
Patients in arm 1 received 1,500 mg of durvalumab as an intravenous infusion and either cisplatin/etoposide, carboplatin/paclitaxel, pemetrexed/cisplatin, or pemetrexed/carboplatin, as well as radiation in 5 fractions per week for about 6 weeks (total 60 Gy). Patients in arm 2 received placebo and 1 of the chemotherapy options along with the radiation regimen.1,2
The primary end point is PFS, and the secondary end points include overall survival (OS), objective response rate, OS at 24 months, rate of complete response, duration of response, disease control rate, time from randomization to second progression, and time to death or distant metastasis.
The trial had an estimated enrollment of 328 patients. Patients were eligible for participation if they had a WHO performance status of 0-1, at least 1 measurable lesion that had not been previously radiated, and a life expectancy of at least 12 weeks. Patients were excluded if they had received prior cancer treatment, had prior exposure to immune-mediated therapy, a history of allogeneic organ transplant, active or prior autoimmune or inflammatory disorders, or any active infection or malignancy.
Durvalumab is being evaluated in other phase 3 trials in ovarian, endometrial, and gastric/gastroesophageal cancers, as well as resectable NSCLC.