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
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Heather A. Wakelee, MD, of Stanford University, Stanford Cancer Institute, discuss new data supporting neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab as a promising new treatment option for patients with resectable stage II, IIIA, or IIIB (N2) non–small cell lung cancer (NSCLC) (Abstract LBA100).
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
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses the efficacy and safety of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, studied for more than 3 years in the BRUIN trial. The results showed that the use of pirtobrutinib continues to have durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma and prior BTK inhibitor therapy. Responses were observed in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations (Abstract 7514).
The ASCO Post Staff
Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss findings from the POLARIX study, which provided the largest prospectively collected circulating tumor DNA (ctDNA) data set on patients with previously untreated diffuse large B-cell lymphoma. Achieving ctDNA-negative status was associated with improved outcomes when patients were treated with polatuzumab vedotin-piiq plus combination chemotherapy vs combination chemotherapy alone (Abstract 7523).
The ASCO Post Staff
Jennifer L. Crombie, MD, of Dana-Farber Cancer Institute, discusses the historically poor outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Her study examined real-world data on the use of novel therapies in this population and found that outcomes with second- and third-line regimens of polatuzumab vedotin-piiq plus bendamustine and rituximab and tafasitamab plus lenalidomide remain suboptimal, with worse outcomes particularly after chimeric antigen receptor T-cell therapy (Abstract 7552).