ADRIATIC trial (ASCO plenary)

Over the last decades, therapeutic advances for patients with limited-stage small-cell lung cancer (LS-SCLC) have been limited. With the current standard of care (i.e., concurrent chemoradiotherapy [cCRT]), the prognosis for these patients is poor with a median overall survival (OS) of 25-30 months and a 3-year overall survival (OS) of about 30%. Inspired by the success of the PACIFIC trial showing an overall survival (OS) benefit with consolidation durvalumab after CRT in patients with unresectable stage III non-small cell lung cancer (NSCLC), the phase III ADRIATIC trial evaluated a similar strategy in patients with LS-SCLC. The results of this study were presented by Dr David Spigel (Sarah Cannon Research Institute, Nashville, TN, USA) during the plenary session of ASCO 2024. We asked Dr Kristof Cuppens, Pulmonologist & Thoracic oncologist at the Jessa Hospital in Hasselt to share his thoughts on these practice changing data.

ADRIATIC is a placebo-controlled randomized phase III trial in which 730 patients with inoperable stage I-III LS-SCLC were randomly assigned to receive durvalumab (1500 mg q4w; N= 264), placebo (q4w; N= 266), or durvalumab in combination with tremelimumab (D 1500 mg q4w + T 75 mg q4w for 4 weeks, followed by D 1500 mg q4w; N= 200). The co-primary endpoints of the study were OS and progression-free survival (PFS) by blinded independent central review (BICR) for patients treated with durvalumab vs. placebo.

After a median follow-up of 37.2 months, consolidation therapy with durvalumab resulted in a median OS of 55.9 months, which is almost 2 years longer than the 33.4-month median OS seen in the placebo arm. This difference in median OS corresponds to a 27% reduced death risk for durvalumab (HR[95%CI]: 0.73[0.57-0.93]; p= 0.0104). Also in terms of PFS, consolidation durvalumab induced a significant benefit over placebo with a median of 16.6 and 9.2 months, respectively (HR[95%CI]: 0.76[0.61-0.95]; p= 0.0161).

The safety profile of consolidation durvalumab was similar to what was seen in PACIFIC, without an increase in the incidence of grade ≥3 (24.4% vs. 24.2%) or serious (29.8% vs. 24.2%) adverse events compared to the control arm. Adverse events led to a treatment discontinuation in 16.4% and 10.6% of durvalumab and placebo treated patients, respectively.

For Dr Cuppens these data establish consolidation durvalumab following cCRT as the new standard of care for patients with LS-SCLC. The benefit in OS and PFS that was obtained with this strategy in ADRIATIC was not only statistically significant, but also clinically relevant, with an absolute increase in 2-year PFS and OS rate of 12% and 8.9%, respectively.