Authors: Joseph Martin, Future Science Group
A recent clinical trial published in the New England Journal of Medicine, presents new data indicating durvalumab improves progression-free survival in patients with stage III non-small-cell lung cancer (NSCLC).
Recent results from a phase III PACIFIC clinical trial presented at the ESMO 2017 Congress (8–12th September 2017, Madrid, Spain) demonstrates the role of durvalumab in the improvement of progression-free survival in patients with locally advanced stage III lung cancer.
PACIFIC is the first phase III trial to test an immune checkpoint inhibitor as sequential treatment in patients with stage III NSCLC who had not progressed following platinum-based chemotherapy concurrent with radiation therapy.
“There is evidence that synergy between radiotherapy and immunotherapy, such programmed death-ligand 1 (PD-L1) inhibitors, could increase the probability of response,” commented first author, Luis Paz-Ares (Hospital Universitario Doce de OctubreWe therefore explored the impact of PD-L1 inhibition after standard chemoradiation treatment.”
This trial specifically compared sequential treatment with the PD-L1 inhibitor durvalumab versus placebo in patients with locally advanced, unresectable stage III NSCLC who had not progressed following platinum-based chemotherapy concurrent with radiation therapy.
The trial is being conducted at 235 centres in 26 countries, and Dr Scott Antonia from the Moffitt Cancer Center (FL, USA) is the lead investigator. It included 713 patients who were randomized 2:1 to receive durvalumab 10 mg/kg every 2 weeks or placebo for up to 12 months. The co-primary endpoints were progression-free survival and overall survival.
Results from a pre-planned interim analysis at 14.5 months were presented at ESMO. The median progression-free survival was 16.8 months in the durvalumab arm compared to 5.6 months with placebo, with a hazard ratio of 0.52.
“Durvalumab decreased the probability of disease progression of 48%. The improvement was consistent across all patient subgroups that were analysed,” Paz-Ares explained.
Interestingly, secondary endpoints of time to death or distant metastasis and objective response rate were also improved across subgroups with durvalumab compared to the placebo. Despite the survival data being immature, it will be further analyzed after a longer period of follow-up.
Treatment-related adverse events occurred in 68% of patients in the durvalumab group compared to 53% in the placebo group. The rate of immune-mediated adverse events was 24% with durvalumab and 8% with placebo. Severe pneumonitis (grade 3/4) occurred in 3.4% and 2.6% of patients on durvalumab and placebo, respectively. Treatment had to be discontinued due to pneumonitis in 6.3% of patients on durvalumab and 4.3% on placebo.
“Overall there was a slight increase in toxicity in the durvalumab arm but severe toxicity was similar between groups,” commented Paz-Ares.
Paz-Ares continued: “Durvalumab is a reasonably well tolerated treatment with a manageable safety profile that improved progression-free survival by 11 months. PD-L1 inhibition after chemoradiation appears to be a new option for patients with locally advanced, unresectable stage III lung cancer. It will be important to see the impact on overall survival after a longer follow-up.”
Pilar Garrido (Ramón y Cajal University Hospital, Madrid Spain), commented on the results for ESMO : “PACIFIC is one of the largest clinical trials recruiting patients with unresectable stage III NSCLC. Giving durvalumab after finishing chemoradiation improved progression-free survival by three-fold compared to placebo, which is a clinically relevant benefit. The results for 12 and 18-month progression-free survival were also highly encouraging.”
Garrido continued “Overall survival data are awaited, but the magnitude of progression-free survival benefit supports this combination as a new standard of care for unresectable stage III NSCLC patients who had no progression following standard care with platinum-based chemotherapy and concomitant radiotherapy.”
Sources: ntonia S.J., Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. N. Engl. J. Med. DOI: 10.1056/NEJMoa1709937 (2017); http://esmo.org/Conferences/ESMO-2017-Congress/Press-Media/Press-Releases/Durvalumab-Improves-Progression-free-Survival-in-Stage-III-Lung-Cancer