Immunotherapy has become pivotal at various stages of GU cancer. This article will provide some updates from the ASCO 2023 conference regarding the efficacy of the same as well as some other newer and older drugs.

THOR trial

1. The efficacy of erdafitinib versus the investigator's choice of chemotherapy (docetaxel or vinflunine) was tested in patients with advanced urothelial cancer with FGFR2/3 aberrations whose disease previously failed to respond on 1 or 2 prior lines of treatment including immunotherapy.
2. The median overall survival (OS) was 12.1 months in Erdafitinib arm versus 7.8 months in the chemotherapy arm with a hazard ratio (HR) of 0.64 and p-value of 0.05. The median progression-free survival (PFS) was 5.6 months in the study arm compared to 2.7 months in the control arm with an HR of 0.58 which was statistically significant.
3. Overall response rates with erdafitinib were 46% versus 12% with chemotherapy. Survival benefits were observed across multiple subgroups, including FGFR alteration type, lines of prior treatment, and primary tumour location.
4. Serious treatment-related adverse events (TRAEs) were observed in only 13% of patients randomly assigned to intervention versus 24% randomly assigned to chemotherapy.
5. However, the frequency of FGFR2/3 mutations in this population is relatively limited, ranging from 10% to 20%, thus reducing the generalisability of the study's findings. Thus, all patients with advanced urothelial cancers should be tested for FGFR mutations for possible addition of erdafitinib.

VESPER trial

1. 437 patients were randomised to receive neoadjuvant chemotherapy with either four cycles of gemcitabine and cisplatin, one every 3 weeks, prior to surgery (84% received all four) or six cycles of dose-dense MVAC, one every 2 weeks, before surgery (60% received all six). 56 patients were randomized in an adjuvant setting.
2. The 5-year overall survival rate was 64% with dose-dense MVAC versus 56% with gemcitabine/cisplatin (P = .078), and the 5-year disease-specific survival was 72% versus 59%, respectively (P =.004).

CONTACT 3 trial

1. This is a multicenter, randomised, open-label study of 522 patients with inoperable, locally advanced, or metastatic clear cell or nonclear cell renal cell carcinoma (RCC ) with or without a sarcomatoid component who experienced radiographic tumour progression during or after immune checkpoint inhibitor treatment in the metastatic setting.
2. Patients were randomly assigned 1:1 to intravenous atezolizumab (1,200 mg every 3 weeks) plus oral cabozantinib (60 mg daily) or the same cabozantinib regimen alone. Treatment continued until loss of clinical benefit or intolerable toxicity.
3. There was no difference between treatment arms in OS and PFS, There was a higher rate of grade 3/4 adverse events (AEs) with the addition of atezolizumab to cabozantinib versus cabozantinib alone (55.3% vs 47.3%).

KEYNOTE B61 study

1. 158 patients with stage IV non clear cell RCC were enrolled to receive pembrolizumab at 400 mg every 6 weeks for up to 18 cycles (2 years) plus lenvatinib at 20 mg once daily, or until disease progression or unacceptable toxicity; lenvatinib could be continued beyond 2 years.
2. The primary endpoint of confirmed objective response on independent central review was achieved in 49% of patients, with complete response in 6%. An additional 33% of patients had stable disease, yielding a disease control rate of 82%. The median duration of response was not reached (95% CI = 13.8 months to not reached), with 75% of responses persisting at 12 months.
3. Grade 3 or 4 treatment-related adverse events occurred in 51% of patients, most commonly hypertension (23%), proteinuria (4%), and stomatitis (4%) .

TALAPRO study

1. 399 patients with homologous recombination repair (HRR)-deficient mCRPC were randomly assigned to receive first-line treatment with talazoparib at 0.5 mg daily (n=200) or placebo (n=199) in addition to enzalutamide at 160 mg daily.
2. Patients in the talazoparib arm had a 55% lower risk of radiographic progression or death than patients in the placebo arm. The median rPFS was not reached in the talazoparib arm and was 13.8 months in the placebo arm (hazard ratio [HR], 0.45; 95% CI, 0.33-0.61; P <.001).
3. Among patients with BRCA alterations, talazoparib was associated with an 80% lower risk of radiographic progression or death (HR, 0.20; 95% CI, 0.11-0.36; P <.001) Although the overall survival (OS) data are immature, there was a favorable trend toward improved OS in the talazoparib arm.
4. The median OS was not reached in the talazoparib arm and was 33.7 months in the placebo arm The most common TRAEs leading to dose reductions in the talazoparib arm were anemia (42.9%), neutropenia (15.2%), and thrombocytopenia (5.6%). Thus, Talazoparib is poised to be part of the upfront treatment of HRR deficient particularly BRCA mutated mCRPC.

To learn more about ASCO highlights, click on the following links:

1. Breast Cancer: Key Highlights from the 2023 ASCO Conference

2. Key ASCO Highlights on Lung Cancer

3. Gastrointestinal cancer: Highlights from ASCO 2023

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bipinesh Sansar, DM Medical Oncology, Associate Professor Medical Oncology at MPMMCC and HBCH, Varanasi.