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.
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Jonathan W. Riess, MD, of the University of California, Davis Comprehensive Cancer Center, explores the findings of three important clinical trials in lung cancer treatment: whether to incorporate immune checkpoint inhibitors into the treatment of EGFR-mutated lung cancer, the importance of central nervous system activity in EGFR-mutant lung cancer, and new therapies for disease with EGFR exon 20 insertion.
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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
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The ASCO Post Staff
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
