Dr. Jessica Geiger from Cleveland Clinic presented an abstract at ASCO 2023 highlighting the potential of Enfortumab vedotin as a novel therapeutic option for head and neck cancer (HNC) patients with recurrent metastatic disease who have failed standard frontline treatments. This patient population faces a significant unmet need, as current treatments have limited efficacy. Enfortumab vedotin, an antibody drug conjugate, targets the Nectin-4 protein expressed in a majority of HNC patients and delivers intracellular chemotherapy to destroy cancer cells.
The EV-202 study, a phase 2, single-arm, multi-cohort trial, enrolled heavily pretreated HNC patients who had exhausted standard treatment options such as platinum chemotherapy and PD-1 inhibitors. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival, progression-free survival, and disease control rate (DCR). In the HNC cohort, Enfortumab vedotin demonstrated an ORR of 24%, which is considerably higher than the single-digit response rates seen with current standard treatments. The DCR was over 50%, indicating significant clinical benefit for a majority of patients.
Although the median duration of response (DOR) and progression-free survival were modest (3-4 months and 6–7 months, respectively), some patients exhibited durable responses. The study’s future directions involve identifying biomarkers or patient characteristics that may predict better response rates. Common adverse events associated with Enfortumab vedotin included skin rash, peripheral neuropathy, and myelosuppression, with grade ≥3 adverse events primarily related to myelosuppression.
The study results are encouraging, providing hope for a successful novel therapy for HNC patients. Further investigations are warranted to explore the potential of Enfortumab vedotin in earlier treatment lines, possibly in combination with immunotherapy. Identifying predictive biomarkers, such as Nectin-4 expression levels, HPV status, and PD-L1 status, is crucial to optimize patient selection. Overall, the study emphasizes the urgent need to address the unmet medical needs in recurrent metastatic HNC and highlights the importance of enrolling patients in clinical trials to advance the field.
In conclusion, Enfortumab vedotin demonstrates promise as a potential treatment option for heavily pretreated HNC patients who have failed standard therapies. The study’s findings suggest a significant clinical benefit with higher response rates than currently available treatments. Further research and exploration are required to unlock the full potential of Enfortumab vedotin, improve patient selection, and potentially integrate it into earlier treatment regimens for HNC. Participating in clinical trials remains essential in advancing the field and addressing the unmet needs of this patient population.