Proffered paper session: GU Tumours non-prostate

In this video, Dr Annelies Verbiest, medical oncologist at the University hospital Antwerp shares the results of 5 clinical trials that were presented in a first of two proffered paper session on non-prostate, genitourinary cancers at ESMO 2024.

In the phase III TiNivo-2 study, a total of 343 patients with clear-cell renal cell carcinoma (ccRCC) who progressed on an immune checkpoint inhibitor (ICI)-based therapy were treated with a combination of nivolumab and tivozanib or tivozanib alone. With a median progression-free survival (PFS) of 5.7 months for the nivolumab-tivozanib combination and 7.4 months for tivozanib alone, the study did not meet its primary endpoint (HR[95%]: 1.10[0.82-1.43]).1 As such, these findings are in line with the results of the CONTACT trial, reaffirming that rechallenge with an ICI in combination with a tyrosine kinase inhibitor (TKI) does not improve outcomes in RCC patients who progressed on a prior ICI-based therapy.

The phase II SUNNIFORECAST study compared the potential of dual ICI therapy with ipilimumab-nivolumab (ipi-nivo) to standard of care (SoC) as first line therapy for patients with non-clear-cell (ncc)RCC. At 12-months, the overall survival (OS) rate with ipi-nivo was reported at 86.9% as compared to 76.8% with SoC (p= 0.0141). The ORR with ipi-nivo was 32.8% vs. 19.6% with SoC. While this study demonstrated a benefit for ipi-nivo in this study, it has to be underscored that the SoC that was used here is not optimal (TKI monotherapy).2 Therefore, the combination of an ICI and a TKI (e.g. lenvatinib-pembrolizumab) is probably the better choice in the first line setting, with ipi-nivo as an alternative for patients in whom an ICI-TKI combination is not an option.

The phase III LITESPARK-005 study previously showed that the HIF-2α inhibitor belzutifan significantly improves the PFS and objective response rate (ORR) compared to everolimus in advanced ccRCC patients who previously received an ICI and an antiangiogenic agent. Unfortunately, updated results of this trial show that this did not translate into a better OS (median 21.4 vs. 18.2 months (HR[95%CI]: 0.92[0.77–1.10]; p= 0.18). At two years, the OS rate reached 45.2% with belzutifan which was fairly similar to the 41.2% 2-year OS rate seen with everolimus.3 Several studies are currently underway evaluating combinations of belzutifan with other treatment modalities in earlier treatment lines for RCC patients.

The proffered paper session also featured a second study evaluating a HIF-2α inhibitor. In this phase I/II study, NKT2152 demonstrated robust anti-tumor activity in a cohort of heavily pretreated advanced ccRCC patients (ORR: 24%, median PFS: 7.5 months). This promising clinical activity in combination with a manageable safety profile warrants further investigation of this agent in this setting.4

Finally, data were presented of a phase I study evaluating a bispecific antibody-drug conjugate (ADC) targeting EGFR and HER3 (BL-B01D1) in patients with advanced urothelial cancer.5 With an ORR of ~40% in a cohort of heavily pretreated patients, increasing to 80% in patients who received this agent in second line, this agent deserves further investigation in a randomized controlled setting.