GEMSTONE-301 Update Confirms Sugemalimab PFS Benefit In Stage III Unresectable NSCLC

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Updated findings from the GEMSTONE-301 trial may support use of the PD-L1 inhibitor sugemalimab in patients with stage III unresectable non-small-cell lung cancer (NSCLC) who have not progressed after concurrent (c) or sequential (s) chemoradiotherapy (CRT). 

The final analysis for the primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) was presented at the IASLC World Conference on Lung Cancer 2022 in Vienna, Austria, by Yi-Long Wu, from Guangdong Provincial People’s Hospital in Guangzhou, China. 

At the cutoff date in March 2022, the median PFS was 10.5 months for the 255 patients who were randomly assigned to receive sugemalimab 1200 mg every 3 weeks for up to 2 years. This compared with a median of 6.2 months for the 126 patients who instead received placebo, giving a significant stratified hazard ratio (HR) of 0.65. 

This “is in line” with the preplanned interim PFS analysis that was previously reported in The Lancet Oncology, the presenter said.  

At 12 months, 49.5% of sugemalimab-treated patients were alive and free from progression, as were 32.3% of those given placebo. The rates after 24 months and 36 months were 38.6% versus 23.1%, and 26.1% versus 0.0%, respectively. 

The majority of patients received cCRT, while 33.7% of sugemalimab and 32.5% of controls were given sCRT. 

When BICR-assessed PFS was examined by type of CRT, the researchers found a trend towards better PFS for patients who received cCRT followed by sugemalimab rather than placebo (median 15.7 vs 8.3 months; stratified HR=0.71), and a significant benefit among those given sCRT followed by sugemalimab (median 8.1 vs 4.1 months; stratified HR=0.57). 

While emphasizing that the overall survival (OS) data have not yet matured and therefore “no formal analysis was performed”, Yi-Long Wu reported that median OS was unreached in the sugemalimab-treated patients versus 25.9 months for those given placebo, giving a stratified HR of 0.69. 

Among patients who had received cCRT, the median OS in the sugemalimab and placebo arms was unreached versus 32.4 months (stratified HR=0.75), and for the patients given sCRT, the corresponding median durations of OS were unreached and 24.1 months (stratified HR=0.60). 

The overall response rates in the full sugemalimab and placebo arms were comparable (24.5 vs 25.2%), but the median duration of response was longer with the PD-L1 inhibitor (24.1 vs 6.9 months), the researcher commented. 

The presenter reported that there were “no new safety signals” in the study and that the safety profile of sugemalimab was “similar” to that of other immunotherapy options. He presented grade 3–5 treatment-related emergent adverse events rates of 11.4% with sugemalimab versus 5.6% with placebo. 

Yi-Long Wu said that the “take home message” from the trial was that “sugemalimab could be safely and effectively used after cCRT or sCRT and become a standard of care in this setting”. 

However, session discussant Linda Martin, from the University of Virginia in Charlottesville, USA, said that when looking at the sCRT and cCRT patient subgroups, the “tiny numbers” of patients who remained at risk in the tail ends of the PFS curve “made it difficult to make too many assumptions” and that the PACIFIC trial of durvalumab had achieved “much more robust numbers and reasonably similar outcomes.” 

Indeed, she questioned why the study investigators had chosen to compare sugemalimab with placebo when durvalumab had been granted approval in this patient population, based on the PACIFIC trial results, before the GEMSTONE-301 trial began. 

Moreover, the discussant queried why approximately a third of patients in the study had received sCRT, noting that all participants fulfilled the ECOG performance status of 0–1 criteria and therefore did not meet the frailty criteria indicating use of sCRT instead of cCRT. 

Linda Martin postulated that the current study findings may better reflect “the superiority of concurrent over sequential CRT” rather than the benefit of sugemalimab per se, and that PFS might have been improved by greater use of cCRT in the study regardless of sugemalimab receipt. 

She therefore concluded that sugemalimab after CRT was “not clearly better” than the current standard of care durvalumab. 

Reference 

OA02.05: Wu Y-L, Zhou Q, Chen M, et al. Sugemalimab vs placebo after concurrent or sequential chemoradiotherapy in patients with unresectable stage III NSCLC (GEMSTONE-301): Final progression-free survival analysis of phase 3 study. IASLC World Conference on Lung Cancer 2022; Vienna, Austria: 6–9 August.