EV+P nearly doubled median PFS and OS versus platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer in the phase 3 EV-302 trial and is NCCN category 1 and ESMO guidelines preferred treatment option. PRO assessments included the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), and the Brief Pain Inventory Short Form (BPI-SF) completed at baseline, weekly for 12 weeks, then every 3 weeks through survival follow-up, inclusive of the time post-progression. This is the unique aspect of the PRO collection as typically PRO collection stops at the end of treatment. Time to pain progression and mean change from baseline in worst pain at week 26 using the BPI-SF were prespecified analyses statistically tested using a gatekeeping strategy. Mean change from baseline through week 26 and time to confirmed deterioration of EORTC-QLQ-C30 and BPI-SF domains were prespecified descriptive analyses. Time to pain progression and time to confirmed deterioration were assessed using Kaplan-Meier methods. Patients with moderate-severe pain at baseline (around 1/3rd) were of special interest and those treated with EV+P had a meaningful improvement from baseline in BPI-SF worst pain from weeks 3 through 26. The Global Health Status (GHS) and QOL was improved with EV+P for both cisplatin-eligible and cisplatin-ineligible patients and outperformed platinum chemotherapy.
Key Takeaways
- EV+P significantly improves PFS and OS compared to platinum-based chemotherapy without detriment to quality of life and functioning.
- Patients with moderate to severe pain treated Ev+P demonstrated clinically meaningful improvements in worst pain and GHS/QOL.
- Data collection across the entire patient journey was a notable approach and was associated with differences in compliance between treatment arms. Findings from this study may inform the design of future trials. Patient-reported outcome data presented here complement the published clinical efficacy and safety data, add the patient perspective, and support the use of enfortumab vedotin + pembrolizumab for patients with previously untreated locally advanced or metastatic urothelial cancer.
The CheckMate 901 (NCT03036098) is a phase 3, multinational, open-label trial of Nivo-GC vs GC for up to 6 cycles, followed by nivolumab maintenance (at a dose of 480 mg) every 4 weeks for up to 2 years.
Presented was a post hoc analysis of the subset of patients who had CR and lymph node-only metastatic disease, a known favorable prognostic factor in UC. A total of 102/608 (16.8%) patients randomized achieved a CR, of whom 54 treated with Nivo-GC, and 56 in the GC alone group had lymph node-only mUC. The median OS in patients with lymph node-only mUC was 46.3 months with Nivo-GC vs 24.9 months with GC, and PFS was 30.5 months vs 8.8 months, respectively.
This analysis shows durable responses in combination in lymph node-only mUC patients.
Perioperative Sacituzumab Govitecan (SG) Alone or in Combination with Pembrolizumab (Pembro) for Patients with Muscle-Invasive Urothelial Bladder Cancer (MIBC): SURE-01/02 Interim Results.3
SURE is a multi-cohort, open-label, phase 2 trial evaluating neoadjuvant SG in MIBC patients who were cisplatin-ineligible either as, monotherapy (SURE-01 trial, NCT05226117) or in combination with pembrolizumab, followed by postsurgical adjuvant pembrolizumab (SURE-02 trial, NCT05535218).
Patients with cT2-4N0M0 UC and ineligible for or refused neoadjuvant cisplatin-based chemotherapy received four 3-weekly cycles of SG at a dose of 10 mg/Kg on days 1 and 8 and subsequently underwent a radical cystectomy. The primary endpoint was ypT0N0 rate. Secondary endpoints included ypT≤1N0 rate, EFS, OS, and safety. In the overall cohort of 21 patients, any grade treatment-related adverse events (TRAE) were observed in 81% of patients; grade 3 TRAEs in 33.3%, and grade 4 TRAEs in 19.1% of patients. One patient experienced a treatment-related death from sepsis. The most common grade ≥3 TRAEs were neutropenia and diarrhea.
Eighteen out of twenty-one patients completed all 4 cycles of SG; 11/18 patients underwent RC and 7 patients refused RC ( 6 due to clinical CR). The median time from end of SG to surgery was 6.9 weeks, pCR was seen in 4/11 (36.4%) and any ypT≤1N0 response was observed in patients (45%). One patient had disease relapse/progression during or post-SG. The protocol was amended to reduce dose of SG to 7.5 mg/kg and mandating primary G-CSF prophylaxis.
Written by: Shilpa Gupta, MD, Director of the Genitourinary Medical Oncology, Taussig Cancer Institute, Co-Leader of the Genitourinary Oncology Program, Cleveland Clinic, Cleveland, OH
References:
- Shilpa Gupta et al., Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC). JCO 42, 4502-4502(2024). DOI:10.1200/JCO.2024.42.16_suppl.4502.
- Galsky, Matt & Sonpavde, Guru & Powles, Thomas & Claps, Melanie & Burotto, Mauricio & Schenker, Michael & Sade, Juan & Bamias, Aristotle & Beuzeboc, Philippe & Bedke, Jens & Oldenburg, Jan & Ürün, Yüksel & Ye, Ding-Wei & Valderrama, Begoña & Tomita, Yoshihiko & Filian, Jeiry & Wang, Lily & Purcea, Daniela & Heijden, Michiel. (2024). Characterization of complete responders to nivolumab + gemcitabine-cisplatin vs gemcitabine-cisplatin alone and patients with lymph node–only metastatic urothelial carcinoma from the CheckMate 901 trial. Journal of Clinical Oncology. 42. 4509-4509. 10.1200/JCO.2024.42.16_suppl.4509.
- Antonio Cigliola et al., Perioperative sacituzumab govitecan (SG) alone or in combination with pembrolizumab (Pembro) for patients with muscle-invasive urothelial bladder cancer (MIBC): SURE-01/02 interim results. JCO 42, LBA4517-LBA4517(2024). DOI:10.1200/JCO.2024.42.17_suppl.LBA4517