Proffered paper session

In this video, Prof Dr Els Van Nieuwenhuysen, gynaecological oncologist at the University Hospitals Leuven discusses four clinical trials that were presented during the proffered paper session on gynaecological cancer at ESMO 2024.

The randomized phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 evaluates the addition of pembrolizumab to adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. For this study, high-risk disease was defined as a FIGO (2009) surgical stage I/II, non-endometrioid cancer with myometrial invasion, FIGO (2009) surgical stage I/II disease of any histology with known aberrant p53 expression or TP53mutation with myometrial invasion, or  FIGO (2009) surgical stage III/IVA disease of any histology.¹ The addition of pembrolizumab to the adjuvant regimen did not lead to a better disease free survival (DFS) in the intent-to-treat (ITT) population, with a HR of 1.05 (95%CI: 0.79-1.32). However, a pre-specified subgroup analysis did show a clinically meaningful DFS benefit with adjuvant pembrolizumab in the subgroup of patients with dMMR/MSI-H disease, with a 2-year DFS rate of 92% in the pembrolizumab-chemotherapy arm as compared to 80% with placebo-chemotherapy (HR[95%CI]: 0.31[0.14-0.69]).¹

The randomized, phase III PRIMA/ENGOT-ov26/GOG-3012 trial previously showed that first line maintenance therapy with niraparib significantly prolongs the progression-free survival (PFS) of patients with newly diagnosed advanced ovarian cancer who obtained a complete (CR) or partial response (PR) following platinum-based chemotherapy. Updated results of this trial presented at ESMO show that this delayed disease progression induced by maintenance niraparib does not lead to a significant benefit in overall survival (OS) (median OS: 46.6 vs. 48.8 months; HR[95%CI]: 1.01[0.84-1.23]). Also when evaluating the data in function of the homologous repair deficiency status the study failed to show an OS benefit with maintenance niraparib.²

The phase I/II TROPHAMET study evaluated the efficacy of avelumab in combination with methotrexate for the treatment of patients with gestational trophoblastic tumors (GTT), a are rare tumor type that develops from the placenta during pregnancy. The study included a total of 26 women with low-risk GTT (FIGO ≤6) with an indication for 1^st line therapy with methotrexate. The combination of avelumab and methotrexate was well-tolerated and proved to be associated with an impressive disease cure rate (i.e., normalization of the hCG level) of 96.2%. This compares favorably to the historical 70% cure rate that is seen with methotrexate alone. After a median follow-up of 24.8 months, none of the patients in the study suffered a recurrence, despite discontinuation of treatment which indicates that their disease is likely cured.³

Finally, ESMO 2024 featured the results of the phase III ATHENA-COMBO trial comparing the combination of rucaparib and nivolumab to rucaparib alone as maintenance treatment for women with newly diagnosed, stage III-IV advanced ovarian cancer who completed platinum-based chemotherapy (CR or PR) and surgery. The study failed to meet its primary endpoint and even showed a worse PFS with the combination of nivolumab and rucaparib vs. rucaparib alone (median: 15.0 vs. 20.2 months; HR[95%CI]: 1.29[1.0-1.53]). Furthermore, the combination treatment also came with a higher incidence of grade ≥3 adverse events (74.6% vs. 63.8%).⁴