Top Takeaways on Key GU Research From the 2021 ESMO Congress

We spotlight key data presented during the 2021 ESMO Congress in kidney cancer, prostate cancer, and bladder cancer.

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.