The standard treatment for advanced/recurrent endometrial cancer (A/R EC) consists of chemotherapy with carboplatin and paclitaxel. Unfortunately, most patients will relapse within a year. The results of the RUBY trial, reported at the ESMO Virtual Plenary on 27th March 2023, showed that adding dostarlimab to chemotherapy significantly improves progression-free survival in A/R EC patients, especially in those with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). Additionally, an early trend toward improved survival was observed in all subgroups. Based on these results, dostarlimab plus chemotherapy could become a novel new of care for these patients.
Endometrial cancer ranks as the sixth most common cancer in women worldwide, with over 400,000 new cases per year. Localised disease is curable with surgery, with a 5-year survival rate of 96%. However, in advanced disease, 5-year survival rates drop to 20%. At present, chemotherapy with carboplatin and paclitaxel remains the standard treatment for these patients. Unfortunately, and although this regimen is effective in nearly 50% of patients, most progress within a year. In recent years, the use of immunotherapy, including anti-PD-1 agents, combined with chemotherapy, has improved the outcomes in multiple tumour types. Based on this rationale, the RUBY trial aimed to evaluate the safety and efficacy of combining the anti-PD-1 agent dostarlimab with carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer (A/R EC), as compared to chemotherapy alone.1
The global phase 3 RUBY trial enrolled 494 patients with primary advanced stage III or IV ED, or patients in first recurrence. These patients were randomly assigned (1:1) to receive dostarlimab or placebo, both in combination with carboplatin/paclitaxel (chemo) followed by dostarlimab or placebo, respectively. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Exploratory analysis of PFS in patients with “hot” tumours (deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H)) and “cold” tumours (mismatch repair proficient [MMRp] or microsatellite stable [MSS]) were also performed.2
After a median follow-up of 25 months, dostarlimab + chemo significantly improved the PFS compared to chemotherapy alone (11.8 vs. 7.9 months, respectively; HR[95%CI]: 0.64[0.507-0.800]; p<0.0001). In the subgroup of patients with “hot” tumours, there were very few cancer progressions among patients receiving dostarlimab + chemo (median PFS could not be estimated). In contrast, the median PFS was reported at 7.7 months in the chemo group (HR[95%CI]: 0.28[0.162-0.495], p<0.0001). In the subgroup of patients with “cold” tumours, the median PFS was 9.9 vs. 7.9 months in the patients receiving dostarlimab + chemo and chemo, respectively (HR: 0.76[0.592-0.981]). There was an early, favourable trend for OS in the combination arm. In the dostarlimab + chemo group, 71.3% of patients were alive at 24 months vs. 56% in the chemo group. Among patients with ‘hot’ tumours, the 2-year OS rates were 83.3% and 58.7%, respectively. In patients with ‘cold’ tumours, OS was 67.7% and 55.1%, respectively. There were no unexpected safety issues with dostarlimab + chemo, and there was evidence for an improved quality of life in patients receiving the combination.1,2
The results of the RUBY trial show an unprecedented improvement in PFS when adding immunotherapy to standard chemotherapy in patients with A/R EC. This benefit was particularly pronounced in patients with so-called ‘hot’ endometrial tumours with dMMR/MSI-H. This benefit was maintained for at least two years, with an early trend for an improved OS. As a result of these promising outcomes, the combination of dostarlimab and chemo represents a potential new standard of care for patients with newly diagnosed primary A/R EC.1,2