Shilpa Gupta, MD, on Urothelial Carcinoma: Long-Term Outcome of Enfortumab Vedotin Plus Pembrolizumab
2023 ASCO Annual Meeting
Shilpa Gupta, MD, of Cleveland Clinic, discusses the results from the EV-103 study and the unmet need for effective first-line therapies in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. After nearly 4 years of follow-up, the trial findings showed that enfortumab vedotin-ejfv plus pembrolizumab continues to demonstrate promising survival trends with rapid and durable responses in this population (Abstract 4505).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Shilpa Gupta, MD:
We are reporting the four-year follow-up of EV103 dose escalation in cohort A. This was the study in locally advanced and metastatic urothelial cancer patients who are ineligible to receive cisplatin and received a combination of enfortumab vedotin and pembrolizumab. Enfortumab vedotin is an ADC, which is already approved in the refractory setting in metastatic urothelial cancer. Previous data has led to the X-rated approval of this combination in this setting. This is the long-term data that is being reported, and we saw that the response rates by BICR was 73.3%. Median overall survival was 26 months at a median follow-up of 47 months. Median progression-free survival was 12.7 months, and the tail of the curve is still holding strong, and this is really important results for these patient populations where historically, the median overall survival used to be six to nine months.
There were no new signals of toxicity. The key toxicities that we saw with the combination were rash, peripheral neuropathy, fatigue, and these are all manageable. If dose reductions and dose discontinuations are done appropriately, these toxicities do tend to resolve. For example, the rash and the hyperglycemia tend to occur early and resolve very early if dose reductions and dose discontinuations or treatment breaks are given. Peripheral neuropathy takes some time to manifest, around 2.7 months at the median, and can resolve by seven months with dose reductions. We really need to be cautious of these toxicities and manage the patients appropriately, but this is really very important data for this patient population, and the ongoing phase three study of EV302, which is looking at this combination versus standard of care gemcitabine cisplatin, or gemcitabine carboplatin will further establish its efficacy across the board.
The ASCO Post Staff
Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss results from the SWOG S1826 study, which showed that nivolumab and AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free survival vs brentuximab vedotin plus AVD in patients with advanced-stage classical Hodgkin lymphoma. Longer follow-up is needed to assess overall survival and patient-reported outcomes. This trial may be a key step toward harmonizing the pediatric and adult treatment of advanced-stage disease (LBA4).
The ASCO Post Staff
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, discuss results of a biomarker subgroup analysis, showing that sotorasib demonstrated consistent clinical benefit vs docetaxel in all molecularly defined subgroups of patients with pretreated KRAS G12C–mutated advanced non–small cell lung cancer (NSCLC). Although no predictive biomarkers were confirmed, novel hypothesis-generating signals were observed (Abstract 9008).
The ASCO Post Staff
Lisa M. DeAngelis, MD, and Ingo K. Mellinghoff, MD, both of Memorial Sloan Kettering Cancer Center, discuss findings from the INDIGO trial showing that the IDH1/2 inhibitor vorasidenib improves progression-free survival for patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. These data demonstrate the clinical benefit of vorasidenib in this patient population for whom chemotherapy and radiotherapy are being delayed.
The ASCO Post Staff
Funda Meric-Bernstam, MD, of The University of Texas MD Anderson Cancer Center, discusses interim results from the DESTINY-PanTumor02 trial, the first tumor-agnostic global study of fam-trastuzumab deruxtecan-nxki (T-DXd) in a broad range of HER2-expressing solid tumors. This agent showed an encouraging overall response rate, particularly in patients with IHC 3+ expression; durable clinical benefit; and a manageable safety profile in these heavily pretreated patients. T-DXd may be a potential new treatment option for this population (Abstract LBA3000).
The ASCO Post Staff
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ticiana Leal, MD, of Winship Cancer Institute of Emory University, discuss the use of tumor treating fields therapy, in which electric fields disrupt processes critical for cancer cell viability. Already approved by the FDA to treat glioblastoma and mesothelioma, the treatment has extended overall survival in this phase III study of patients with metastatic non–small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, without exacerbating systemic toxicities (Abstract LBA9005).
