Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial

Current challenges of unresectable stage III NSCLC: are we ready to break the glass ceiling of the PACIFIC trial?

“…Grade 3–4 treatment-related AEs occurred in 9% and 6% of the patients in the sugemalimab and placebo arm, respectively, the most common being pneumonitis or immune-mediated pneumonitis (3% in the sugemalimab arm versus <1% of in the placebo arm). 33 Although this trial endorses the role of a consolidation ICI strategy after CTRT, a significant limitation of the GEMSTONE-301 trial is regarding data about PD-L1 expression, as it is missing in half of the patients enrolled, due to PD-L1 expression testing was not an obligatory inclusion step. Finally, the single-arm phase II LUN 14-179 trial (NCT02343952) 34 reported that consolidation pembrolizumab after cCTRT improved time to metastatic disease, PFS, and OS in comparison with historical controls of chemoradiation alone.…”

“…Although cCTRT improves survival compared with sCTRT, more than half of the patients with stage III NSCLC are not eligible for cCTRT. 47 Following the feasibility assessment of durvalumab after sCTRT in PACIFIC-R trial 31 and sugemalimab in the GEMSTONE-301 trial [HR for PFS in sCTRT 0.59 (95% CI: 0.39–091) and in cCTRT 0.66 (0.44–0.99)], 33 the cohort 1 of the PACIFIC-6 trial (NCT03693300) also assessed the safety and tolerability of durvalumab (1500 mg every 4 weeks, Q4W up to 2 years) after sCTRT in patients with ECOG PS ≤2. The primary endpoint was ssafety defined, as the incidence of treatment related AE grade ≥3.…”

“… 62 For GEMSTONE 301, the percentage of patients completing the 2 years of therapy is still unknown, as at data cutoff, 43% of patients in the sugemalimab arm were still on treatment. 33 This is of particular relevance as in the first-line metastatic setting treatment is up to 2 years in some trials or until disease progression in others. 3 Indeed, it remains unknown whether longer treatment duration correlates with higher benefit from ICI (or is due to bias as patients who progress will have a shorter course of ICI) and whether CTRT modulates the immune system in such a way that a shorter duration of treatment is also feasible.…”

Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches

“…PFS benefit was observed in both the SCRT (median PFS 8.1 versus 4.1 months, HR 0.59) and CCRT groups (median PFS 10.5 versus 6.4 months, HR 0.66). 16 In the single-arm phase II open label PACIFIC-6 trial, 120 patients with Eastern Cooperative Oncology Group PS 2 received adjuvant durvalumab (up to 2 years versus 1 year in PACIFIC), if they did not have progressive disease (PD) after SCRT. The primary endpoint was safety, defined as the incidence of treatment-related AEs (TRAEs) grade !3.…”

Therapeutic revolution for inoperable stage III non-small cell lung cancer in the immune era

“…Surveys have indicated that, although the proportion of patients receiving cCRT in the real world has increased since the publication of the PACIFIC study results, approximately 40%-70% of patients receiving CRT are treated with sCRT in clinical practice in China and several European countries 11,12 . The GEMSTONE-301 study, led by Professor Yilong Wu 13,14 , included patients with EGFR/ ALK-negative, inoperable stage III NSCLC who had no progression after cCRT and sCRT. Patients received consolidation therapy with the anti-PD-L1 monoclonal antibody sugemalimab or placebo for 2 years.…”