Unexpected outcomes from several late-stage trials of adjuvant therapies in solid tumors were presented at the European Society for Medical Oncology (ESMO) Congress 2024, offering critical insights into cancer treatment strategies. While some trials demonstrated positive advancements, others revealed surprising setbacks, prompting a reevaluation of treatment approaches for specific patient populations.
Endometrial Cancer: Pembrolizumab's Subgroup Specific Benefit
The ENGOT-en11/GOG-3053/KEYNOTE-B21 trial assessed the efficacy of adding pembrolizumab to adjuvant chemotherapy in 1,095 patients with newly diagnosed high-risk endometrial cancer. While the addition of pembrolizumab did not improve disease-free survival in the intention-to-treat population (HR = 1.02), a significant improvement was observed in the subgroup with mismatch repair–deficient (dMMR) tumors (HR = 0.31). According to Christian Marth, MD, PhD, of the Medical University of Innsbruck in Austria, this could represent a new standard of care for the dMMR subgroup, suggesting carboplatin, paclitaxel, and pembrolizumab should be considered for adjuvant treatment in dMMR, high-risk endometrial carcinoma.
The trial involved patients who had undergone surgery with curative intent and received adjuvant pembrolizumab (200 mg) or placebo every 3 weeks for six cycles plus carboplatin/paclitaxel, followed by pembrolizumab (400 mg) or placebo every 6 weeks for four or six cycles, with or without radiotherapy. The co-primary endpoints were investigator-assessed disease-free survival and overall survival in the intention-to-treat population. After a median follow-up of 23.9 months, the 2-year disease-free survival rate in the dMMR subgroup was 92% with pembrolizumab versus 80% without.
Hepatocellular Carcinoma: Atezolizumab and Bevacizumab's Fading Benefit
An updated analysis of the IMbrave050 trial, presented by Adam Yopp, MD, of UT Southwestern Medical School in Dallas, showed that the positive results initially observed for adjuvant atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma were not sustained. The study, which initially demonstrated a significant 28% reduction in the risk of recurrence (P = .012) at a median follow-up of 17.4 months, revealed that the recurrence-free survival curves converged around 24 months with longer follow up.
The trial involved maintenance therapy with atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) every 3 weeks for 17 cycles, compared to active surveillance for 1 year. At a median follow-up of 35 months, median recurrence-free survival was 33.2 months with atezolizumab plus bevacizumab and 36.0 months with active surveillance. Despite the lack of sustained benefit, a post hoc analysis indicated a pronounced delaying of recurrence with atezolizumab plus bevacizumab within the first 12 months after resection in some patients. Maeve Lowery, MD, a gastrointestinal oncologist and researcher at Trinity College, Dublin, Ireland, noted that the overall survival outcomes will likely be confounded due to crossover to active treatment and additional resections or ablations.
NSCLC: Durvalumab Fails to Show Significant Improvement
Findings from the phase III CCTG BR.31 trial indicated that adjuvant durvalumab did not significantly improve disease-free survival compared with placebo after resection in patients with early-stage non–small cell lung cancer (NSCLC). With a median follow-up of 60 months, median disease-free survival was about 6 months longer with durvalumab than placebo, but the difference was not statistically significant (HR = 0.89; P = .207). Glenwood Goss, MD, of the University of Ottawa, Canada, noted that there appeared to be no correlation of statistical significance between PD-L1 expression and disease-free survival.
The study included 1,219 adults with completely resected stage IB–IIIA NSCLC who were randomly assigned 2:1 to receive durvalumab or placebo every 4 weeks for 12 months. The primary patient population evaluated in the study had tumors with a PD-L1 expression of 25% or higher. In the overall population, median disease-free survival was approximately 60 months with durvalumab and 54 months with placebo. Dr. Goss highlighted that the control arm in CCTG BR.31 performed better than observed in two similar trials that were positive, potentially accounting for the negative trial result.
