Andrea Apolo, MD
Invited discussant Andrea Apolo, MD, of the National Cancer Institute in Bethesda, Maryland, emphasized that the EV-302/KEYNOTE-A39 and CheckMate 901 trials mark a significant achievement.
“Outperforming chemotherapy in first-line therapy is monumental for our field. The two studies presented are the first trials to challenge the long-standing standard of first-line platinum-based chemotherapy for patients with advanced or metastatic urothelial carcinoma,” Dr. Apolo said.
“CheckMate 901 is the first study to show an improvement in overall survival using a combination of chemotherapy and immunotherapy in patients with metastatic bladder cancer,” she continued. “This is highly encouraging given that previous phase III studies of checkpoint immunotherapy in this disease failed to show a statistical improvement in overall survival. It is interesting to note that patients in CheckMate 901 all received cisplatin, whereas patients in other trials received either carboplatin or cisplatin. It may therefore be that advanced bladder cancer is particularly sensitive to the specific combination of nivolumab and cisplatin.”
Superior Regimen
She emphasized that the enfortumab vedotin-ejfv/pembrolizumab regimen used in EV-302 was superior to nivolumab plus chemotherapy in CheckMate 901, achieving better overall survival, a higher response rate, and a longer duration of benefits. The overall survival benefit in the EV-302 trial was evident across all key subgroups, regardless of PD-L1 status, presence or absence of liver metastases, and cisplatin eligibility.
“The data for enfortumab vedotin and pembrolizumab are particularly impressive, and this combination will clearly become the new standard of cancer care for this cohort of patients,” she stated.
Remaining Questions
Dr. Apolo noted that the new antibody-drug conjugate/immune checkpoint inhibitor combination raises some questions: “How can the toxicity of the combination be reduced? Why do microtubule-destabilizing drugs such as enfortumab vedotin combine so well with checkpoint inhibitors? Can a better understanding of the complementary mechanisms build on the therapeutic activity? Would other cytotoxic payloads work even better? How would the EV-302 combination work in the neoadjuvant or adjuvant setting?”
She concluded: “The field of urothelial carcinoma is evolving, and it is fantastic news that we can now improve survival for our patients. Multiple clinical trials are ongoing, such as the phase III NILE study, which is investigating durvalumab plus chemotherapy vs durvalumab with tremelimumab plus chemotherapy vs chemotherapy alone.”
DISCLOSURE: Dr. Apolo reported no conflicts of interest.
