(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a kidney and bladder cancers poster session. Dr. Terence Friedlander presented the results of an additional 3-months follow-up of the EV-103 Cohort K, which evaluates enfortumab vedotin (EV) with or without pembrolizumab in cisplatin-ineligible, previously untreated locally advanced or metastatic urothelial cancer.
The management of patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma remains clinically challenging due to the paucity of highly effective agents in this setting. As such, there is an unmet need for durable, effective first-line treatment options in this setting. EV and pembrolizumab have each shown survival benefits as monotherapeutic agents in the ≥2nd line setting.1,2 There is evidence from pre-clinical studies to suggest that EV induces immunogenic cell death, which may be synergistically enhanced with the addition of PD-1 inhibitors, such as pembrolizumab. This combination has shown promising results in the initial EV-103 dose escalation/Cohort A report (ESMO 2022), and, as such, formed the basis for this Cohort K data, for which Dr. Friedlander provided updated results.
EV-103 Cohort K included patients with cisplatin-ineligible, locally advanced or metastatic urothelial carcinoma, who were randomized in a 1:1 fashion to either:
- EV monotherapy (1.25 mg/kg, days 1 and 8)
- EV + pembrolizumab (200 mg, day 1 of each 3-week cycle)
The primary outcome was objective response rate (ORR) per RECIST v1.1 criteria, assessed by blinded independent central review. Secondary outcomes included:
- Duration of response
- Disease control rate
- Progression-free survival
- Overall survival
- Safety
Of note, there were no planned statistical comparisons between the two treatment arms.
This cohort included 149 patients, 76 and 73 treated with EV + pembrolizumab and EV alone, respectively. For the EV + pembrolizumab arm, the median follow-up was 17.6 months, with a confirmed ORR of 64.5% (95% CI: 52.7 – 75.1%). The median duration of response was not reached. Secondary outcomes in this arm were as follows:
- Disease control rate: 86.6%
- PFS at 6 and 12 months: 73.8% and 54.5%
- OS at 6 and 12 months: 88.2% and 81.5%
Conversely in the EV monotherapy arm, the confirmed ORR was 45.2%, with a median follow-up of 18.2 months. The median duration of response was 13.2 months. Secondary outcomes were as follows:
- Disease control rate: 79.5%
- PFS at 6 and 12 months: 64.2% and 40.3%; median PFS: 8.2 months
- OS at 6 and 12 months: 83.6% and 69.7%; median OS: 21.7 months
EV treatment-related adverse events of special interest included:
- Skin reactions (EV + pembrolizumab: 67.1%; EV mono: 45.2%)
- Peripheral neuropathy (EV + pembrolizumab, 63.2%; EV mono: 54.8%)
- Hyperglycemia (EV + pembrolizumab: 14.5%; EV mono: 11.0%)
In the EV + pembrolizumab arm, the most frequent (any grade) pembrolizumab treatment-emergent adverse events of special interest were:
- Severe skin reactions (27.6%)
- Hypothyroidism (13.2%)
- Pneumonitis (9.2%).
Dr. Friedlander concluded that with an additional three months of follow-up, the combination of EV plus pembrolizumab continues to demonstrate a high confirmed ORR with rapid and durable responses as first line treatment in cisplatin ineligible, locally advanced/metastatic urothelial carcinoma patients. The safety profile was manageable with no new signals/safety concerns after extended treatment exposure.
Presented by: Terence W. Friedlander, MD, Professor, Chief of Hematology and Oncology, Department of Medicine, University of California, San Francisco Medical Center, San Francisco, CA
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References:1. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021 Mar 25;384(12):1125-1135.
2. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015-1026.