Top Takeaways on Key GU Research From the 2021 ESMO Congress

Kidney Cancer

CheckMate 9ER (NCT03141177): Post-hoc Exploratory Analysis

• Phase 3 trial that evaluated the combination of nivolumab (Opdivo) and cabozantinib (Cabometyx) in patients with untreated advanced renal cell carcinoma (RCC)
• The HR for progression-free survival (PFS) favored nivolumab/cabozantinib over sunitinib regardless of nephrectomy status, with a longer median PFS of 19.4 months vs 8.9 months, respectively, with prior nephrectomy (HR, 0.50; 95% CI, 0.39-0.64) and 11.3 months vs 7.0 months, respectively, without prior nephrectomy (HR, 0.62; 95% CI, 0.43-0.89).
• With prior nephrectomy, the objective response rate (ORR) was 60.8% with nivolumab/ cabozantinib vs 30.5% with sunitinib.
• Without prior nephrectomy, the ORR was 41.6% with nivolumab/cabozantinib vs 23.2% with sunitinib.

KEYNOTE-426 (NCT02853331): Subsequent Treatment Analysis

• Phase 3 study that evaluated the combination of pembrolizumab (Keytruda) and axitinib (Inlyta) vs sunitinib (Sutent) as first-line therapy in patients with advanced clear cell RCC
• The median overall survival (OS) was 45.7 months with the combination vs 40.1 months with sunitinib (HR, 0.73; 95% CI, 0.60-0.88).
• The median PFS was 15.7 months arm with the combination vs 11.1 months in the monotherapy arm (HR, 0.68; 95% CI, 0.58-0.80).
• Among patients who received subsequent anticancer therapy with a PD-1/PD-L1 inhibitor, 21.6% were treated with the combination and 74.4% were treated with sunitinib.
• In the combination arm, 88.2% of patients received a VEGF/VEGFR inhibitor as subsequent treatment vs 68.7% in the sunitinib arm.

Meta-Analysis of Frontline Immunotherapy

• The trials included were the phase 3 CheckMate 9ER trial (NCT03141177), the phase 3 CheckMate 214 trial (NCT02231749), the phase 3 JAVELIN Renal 101 study (NCT02684006), the phase 3 KEYNOTE-426 study (NCT02853331), and the phase 3 CLEAR trial (NCT02811861).
• Frontline combination immunotherapy resulted in improved PFS (HR, 0.64; 95% CI, 0.51-0.82) and OS (HR, 0.71; 95% CI, 0.61-0.84) compared with sunitinib in patients with advanced RCC.

Prostate Cancer

Trial of Sabizabulin (NCT03752099)

• Phase 1b/2 trial that evaluated sabizabulin in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with at least 1 androgen receptor–targeted therapy
• Common adverse effects with the agent included diarrhea, fatigue, and alanine aminotransferase and aspartate aminotransferase level increases, all of which were mostly grade 1 and 2.
• The ORR in the intention-to-treat population was 20.7%, with 5 partial responses and 1 complete response.
• In patients who received at least 63 mg, which was the recommend phase 2 dose, the estimated median radiographic PFS (rPFS) was 7.4 months.

PEACE-1 (NCT01957436)

• Phase 3 trial that evaluated androgen deprivation therapy (ADT) plus docetaxel; ADT plus docetaxel, abiraterone acetate (Zytiga), and prednisone; ADT plus docetaxel and radiotherapy; and ADT plus docetaxel, abiraterone, prednisone, and radiotherapy in patients with metastatic hormone-naïve prostate cancer
• The addition of abiraterone was associated with a statistically significant improvement in rPFS.
• The median rPFS was 4.5 years with abiraterone vs 2.0 years without (HR, 0.50; 95% CI 0.40-0.62; P < .0001).

STAMPEDE (NCT00268476): Combined Analysis

• Phase 2/3 trial that evaluated ADT, abiraterone, and prednisolone (AAP) with or without enzalutamide (Xtandi) vs ADT alone in patients with high-risk nonmetastatic prostate cancer
• Improved metastasis-free survival (MFS) was seen in the AAP-based therapy groups vs the ADT-alone group (HR, 0.53; 95% CI, 0.44-0.64; P = 2.9 × 10^-11).
• The 6-year MFS rate improved from 69% with ADT alone to 82% with AAP-based therapy.
• Improved OS was seen in the AAP-based groups vs the ADT-alone group (HR, 0.60; 95% CI, 0.48-0.73; P = 9.3 x 10^-7).
• The 6-year OS rate improved from 77% with ADT alone to 86% with AAP-based therapy.

COSMIC-021 (NCT03170960)

• Phase 1b study that evaluated the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) in previously treated patients with locally advanced or mCRPC
• The investigator-assessed ORR was 23%; the investigator-assessed ORR in high-risk patients was 27%.
• The median PFS per investigator assessment was 5.5 months in the overall population vs 5.6 months in high-risk patients.
• The median OS with the combination was 18.4 months in the overall and high-risk populations.
• The disease control rate was 84% per investigator assessment; it was 88% among high-risk patients.

Bladder Cancer

NORSE (NCT03473743)

• Phase 2 trial that evaluated the combination of erdafitinib (Balversa) and cetrelimab in patients with newly diagnosed, cisplatin-ineligible, metastatic or locally advanced urothelial carcinoma harboring FGFR alterations
• The ORR was 68% in 19 efficacy-evaluable patients who received the combination vs 33% in 18 patients who received erdafitinib alone.
• Confirmed complete responses were seen in 4 patients and 1 patient, respectively.