As neoadjuvant enfortumab vedotin plus pembrolizumab (EVP) achieves high pathologic complete response rates in MIBC, a critical question emerges: is adjuvant EVP necessary for everyone? Continuing treatment in patients who are already cancer-free post-surgery may offer no extra benefit while increasing toxicity.

In real-world practice, oncologists are granting treatment breaks, or 'holidays,' to metastatic bladder cancer patients who achieve major responses on enfortumab vedotin-pembrolizumab. This practice, driven by toxicity management and quality of life concerns, is common despite the lack of formal trial data to guide the optimal duration or timing of discontinuation.

In the EV+pembrolizumab combination, if a patient achieves an excellent response but develops prohibitive EV-related toxicities like neuropathy, a viable strategy is to discontinue EV and maintain the patient on pembrolizumab monotherapy. This can sustain the response while improving quality of life.

While neoadjuvant pembrolizumab (KEYNOTE-689) is now standard of care for resectable head and neck cancer, it carries a critical risk. During the pre-surgical treatment window, some patients may experience disease progression or toxicity that makes them ineligible for their planned curative surgery.

In the Keynote 522 trial for early-stage TNBC, adding pembrolizumab to chemotherapy resulted in only a modest improvement in pathological complete response (pCR). Surprisingly, this small initial gain translated into much more robust and significant long-term improvements in event-free and overall survival.

KEYNOTE-522 data shows that achieving pathologic complete response (path CR) with pembrolizumab offers a greater survival benefit than achieving path CR with chemotherapy alone. This suggests immunotherapy provides a lasting benefit beyond just initial tumor eradication.

Clinical trial data shows adding a PD-1 inhibitor to BCG for NMIBC yields a small event-free survival benefit of only 6-8%. This modest gain must be carefully weighed against the substantial risk of autoimmune toxicities from two years of immunotherapy, making it a critical shared decision with the patient.

The discontinuation rate for pembrolizumab due to side effects was lower in the LITESPARK 022 trial compared to the earlier Keynote 564 trial (20%). This trend suggests that as clinicians gain more experience with immune checkpoint inhibitors, they are becoming more adept at managing immune-related adverse events, allowing more patients to complete their therapy.

While KEYNOTE-905 showed dramatic survival benefits with neoadjuvant plus adjuvant EV-pembrolizumab, its design makes it impossible to isolate the benefit of each phase. The high (57%) pathologic complete response after neoadjuvant therapy alone suggests many patients may be overtreated with adjuvant cycles, risking unnecessary long-term toxicity like neuropathy.