Tag: Oncology

  • ASCO GU 2026: Perioperative EV/Pembrolizumab Outperforms Gemcitabine/Cisplatin in MIBC

    At the 2026 ASCO Genitourinary Cancers Symposium, Matthew D. Galsky, MD, presented results from the phase 3 KEYNOTE-B15 study showing that perioperative enfortumab vedotin plus pembrolizumab improved outcomes over neoadjuvant gemcitabine plus cisplatin in cisplatin-eligible muscle-invasive bladder cancer (MIBC). The findings are notable because cisplatin-based neoadjuvant chemotherapy has remained the standard of care for eligible patients with MIBC for decades, and KEYNOTE-B15 is the first phase 3 trial to show superior outcomes with a non-platinum perioperative regimen.

    KEYNOTE-B15 enrolled patients with clinically localized muscle-invasive urothelial carcinoma of the bladder who were eligible for cisplatin-based chemotherapy and radical cystectomy. Patients were randomly assigned 1:1 to 4 cycles of neoadjuvant enfortumab vedotin plus pembrolizumab followed by cystectomy and adjuvant pembrolizumab, with the first 5 adjuvant cycles given with enfortumab vedotin, or to 4 cycles of neoadjuvant gemcitabine plus cisplatin followed by cystectomy and observation. Randomization was stratified by PD-L1 status, clinical stage, and geographic region. The primary endpoint was blinded independent central review–assessed event-free survival (EFS), with overall survival (OS) and pathologic complete response (pCR) among the key secondary endpoints.

    A total of 808 patients were randomized between May 2021 and December 2023. With a median follow-up of 33.6 months, EFS was significantly improved with enfortumab vedotin plus pembrolizumab. Median EFS was not reached in the experimental arm vs 48.5 months with gemcitabine plus cisplatin (hazard ratio [HR], 0.53; 95% CI, 0.41-0.70; 1-sided P<.0001). The 24-month EFS rates were 79.4% and 66.2%, respectively. OS also favored enfortumab vedotin plus pembrolizumab (HR, 0.65; 95% CI, 0.48-0.89; 1-sided P=.0029). Median OS was not reached in either arm, and the 24-month OS rates were 86.9% with enfortumab vedotin plus pembrolizumab and 81.3% with gemcitabine plus cisplatin.

    Pathologic complete response rates were higher with the perioperative enfortumab vedotin/pembrolizumab approach. In the intent-to-treat population, centrally assessed pCR was 55.8% with enfortumab vedotin plus pembrolizumab vs 32.5% with gemcitabine plus cisplatin, for an estimated difference of 23.4% (95% CI, 16.7-29.8; 1-sided P<.0001). In the presentation, Galsky noted that among patients who underwent cystectomy, the pCR rate in the enfortumab vedotin plus pembrolizumab arm was 64.4%. The ability to proceed to surgery was similar between arms, at 87% with enfortumab vedotin plus pembrolizumab and 90% with gemcitabine plus cisplatin.

    Safety was consistent with the known profiles of the regimens. Treatment exposure was longer in the enfortumab vedotin plus pembrolizumab arm. Grade 3 or higher treatment-emergent adverse events occurred in 75.7% of patients receiving enfortumab vedotin plus pembrolizumab and 67.2% of those receiving gemcitabine plus cisplatin. The most common grade 3 or higher drug-related adverse event of special interest with enfortumab vedotin was skin reactions.

    Overall, in a cisplatin-eligible population that has long been treated with cisplatin-based perioperative therapy, KEYNOTE-B15 showed improvements in EFS, OS, and pCR with enfortumab vedotin plus pembrolizumab. Together with prior positive perioperative data in cisplatin-ineligible disease, the study supports enfortumab vedotin plus pembrolizumab as a new treatment option across a broader MIBC population.

    References

    1. Galsky MD, Balar AV, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab for patients with muscle-invasive bladder cancer who are eligible for cisplatin-based chemotherapy: randomized, open-label, phase 3 KEYNOTE-B15 study. Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 2026; San Francisco, CA. Abstract LBA630.

  • ASCO GI 2026: Encorafenib/Cetuximab Plus FOLFIRI Improves Response in BRAF V600E CRC

    ASCO GI 2026: Encorafenib/Cetuximab Plus FOLFIRI Improves Response in BRAF V600E CRC

    At the 2026 Gastrointestinal Cancers Symposium, BREAKWATER Cohort 3 delivered the clearest signal yet that encorafenib plus cetuximab can be paired with FOLFIRI (folinic acid [leucovorin], fluorouracil [5‑FU] and irinotecan) in the first-line treatment of BRAF V600E-mutant metastatic colorectal cancer. In the oral presentation, Scott Kopetz, MD, reported a statistically significant improvement in objective response rate with the targeted regimen plus chemotherapy over standard FOLFIRI with or without bevacizumab, with an early overall survival trend that also favored the experimental arm.

    The phase 3, open-label BREAKWATER study has already established the activity of encorafenib and cetuximab with an oxaliplatin backbone. Cohort 3 asked whether the same targeted approach could work with FOLFIRI for patients who are not ideal candidates for oxaliplatin, including those with prior exposure in the adjuvant setting or baseline neuropathy. This cohort enrolled previously untreated patients with microsatellite-stable, BRAF V600E-mutant metastatic colorectal cancer and ECOG performance status 0 or 1. Patients were randomly assigned 1:1 to encorafenib plus cetuximab and FOLFIRI or to control FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate by blinded independent central review. Progression-free survival was the key secondary endpoint, with overall survival, duration of response, and safety among the additional secondary endpoints.

    The confirmed objective response rate was 64% with encorafenib, cetuximab, and FOLFIRI compared with 39% in the control arm, meeting the primary endpoint (one-sided P value, .0011; odds ratio, 2.8). Median follow-up was just over 10 months. Median overall survival was not estimable in either arm, but the reported hazard ratio for overall survival was 0.49, favoring the targeted triplet. Progression-free survival follow-up is ongoing and has not yet been reported for this cohort.

    No new safety signals emerged, with adverse events consistent with those expected for each study drug. Grade 3 or 4 treatment-related adverse events occurred in 63% of patients on the experimental arm and 71% of patients in the control group. Serious treatment-emergent adverse events were reported in 39% of patients treated with encorafenib, cetuximab, and FOLFIRI and in 37% of those in the control arm. Treatment-emergent adverse events leading to permanent discontinuation of any study treatment was 11% in the encorafenib-containing arm and 9% in the control arm. Skin hyperpigmentation, dry skin, asthenia, weight decrease, arthralgia, palmar-plantar erythrodysesthesia, and rash appeared to occur more commonly on the encorafenib-containing arm.

    Overall, these data are encouraging, especially for patients where oxaliplatin is not an ideal fit, but longer follow-up is needed.

    References

    Kopetz S, Wasan HS, Yoshino T, et al. BREAKWATER: Primary analysis of first-line encorafenib plus cetuximab plus FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer. Presented at: Gastrointestinal Cancers Symposium; 2026. Abstract 13.