乌鸦传媒

Another immune checkpoint inhibitor has demonstrated a life-extending benefit in non-small cell lung cancer (NSCLC), according to long-term follow-up in a randomized trial.

Patients with unresectable stage III NSCLC had a median overall survival (OS) of 47.5 months with durvalumab (Imfinzi) versus 29.1 months for patients who received placebo after initial chemoradiation (CRT). Median progression-free survival (PFS) increased threefold, from 5.6 months with placebo to 16.9 months with the PD-L1 inhibitor.

After a median follow-up of 34.2 months, durvalumab-treated patients had an estimated 5-year OS rate of 42.9%, reported David R. Spigel, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee, and co-authors in the .

"Given the unprecedented nature of the findings ... studies have been initiated to investigate the use of durvalumab after sequential CRT or radiotherapy alone (for patients who are chemotherapy ineligible), and durvalumab in combination with novel anticancer agents post-CRT, with the aim of further extending clinical benefit to more patients in this setting," the authors wrote.

The results established "a new benchmark for SoC [standard of care] in this setting," they added. As the is the first study to show improved survival with immunotherapy in a curative-intent setting, the results "established the rationale for further investigation of durvalumab in other curative-intent settings across other cancers."

The updated report backs up the "standard of care" status that durvalumab earned when the initial results of PACIFIC showed a significant survival advantage and threefold improvement in PFS in patients with unresectable stage III NSCLC. The findings also add to the transformative impact of immunotherapy on management of NSCLC.

Authors of a recounted the timeline of practice-changing trials of immunotherapy. Trials involving five different PD-1/L1 inhibitors and the CTLA-4 inhibitor ipilimumab (Yervoy) initially carved out a role for immunotherapy in the salvage setting of metastatic NSCLC before additional studies established PD-1/L1 inhibitors as the first-line SoC. The PACIFIC trial established durvalumab as the standard for inoperable stage III NSCLC. Ongoing trials are evaluating immunotherapy in combination with targeted therapies and in the neoadjuvant and adjuvant settings for patients with operable disease.

The emergence of long-term data from early trials of immunotherapy have confirmed the durability of survival benefits in NSCLC. A trial of nivolumab (Opdivo) in previously treated metastatic NSCLC showed a sixfold difference in 5-year OS.

A randomized trial of pembrolizumab (Keytruda) versus chemotherapy in previously treated advanced NSCLC showed almost a 20% absolute difference in 3-year OS in favor of immunotherapy among patients with high PD-L1 expression. An updated analysis showed a 5-year OS rate of 31.9% in the pembrolizumab group versus 16.3% in patients who received chemotherapy.

PACIFIC involved patients with unresectable stage III NSCLC that had not progressed after initial CRT. Participants were randomized 2:1 to consolidation therapy with durvalumab or placebo for a maximum of 12 months. The primary endpoints were OS and PFS. The updated report focused on exploratory analyses of survival after 5 years of follow-up. Median follow-up was 34.2 months for all patients and 61.6 months for censored patients.

The results showed an 18.4-month absolute difference in median OS, which translated into a 28% reduction in the survival hazard in favor of durvalumab (95% CI 0.59-0.89). The 11.3-month absolute difference in median PFS represented a 45% decrease in the hazard for disease progression or death (95% CI 0.45-0.68).

The exploratory analysis of 5-year OS favored durvalumab (42.9% vs 33.4%) but was associated with overlapping confidence intervals (38.2% to 47.4% vs 27.3% to 39.6%). Comparison of 5-year PFS revealed a significant advantage in favor of durvalumab (33.1% vs 19.0% with non-overlapping 95% confidence intervals).

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