The emergence of positive data from trials like PATINA creates a dilemma for oncologists treating patients who are already stable on an older maintenance therapy. The consensus suggests not altering a successful regimen to avoid disrupting patient stability, revealing a cautious approach to integrating new evidence into established care.

Data from the Podium 303 crossover arm shows that giving retafanilumab monotherapy after progression on chemotherapy yields a dismal 5.8% response rate. This confirms that the synergistic effect of combining chemo and immunotherapy upfront is critical and cannot be replicated by sequential treatment.

The NCI 9673 trial demonstrated that adding the CTLA-4 inhibitor ipilimumab to the PD-1 inhibitor nivolumab did not improve response rate, PFS, or overall survival in patients with previously treated anal cancer. This finding discourages this combination approach, avoiding unnecessary toxicity.

Data from the Podium-303 trial's crossover arm suggests that waiting to use a PD-1 inhibitor after progression on chemotherapy is less effective than using it concurrently from the start. This supports the synergistic effect of chemo-immunotherapy and favors the concurrent approach as the standard of care.

Traditional endpoints like progression-free survival (PFS) incentivize continuous treatment. The NCI group proposes "treatment-free survival," a novel metric that quantifies time spent *off* therapy. This endpoint better captures the patient experience and rewards treatments that provide durable responses after a finite course.

For patients with oligometastatic disease who achieve a deep PSA response (e.g., to zero), oncologists consider finite treatment durations (e.g., 18-24 months) followed by observation. This "do less harm" approach challenges the standard of continuous therapy until progression, aiming for long-term treatment-free intervals.

In the Podium-303 trial, adding retifanlimab to chemotherapy improved the overall response rate by 11%. However, its most significant impact was doubling the median duration of response from 7.2 to 14 months, providing a much more durable benefit for patients after chemotherapy is stopped.

A common clinical pitfall is treating RAS/BRAF wild-type anal cancer with anti-EGFR antibodies, extrapolating from rectal adenocarcinoma protocols. Retrospective data shows this approach has only modest efficacy (4-5 month PFS) and is not a recommended strategy, highlighting a key difference between the two diseases.

While the POD1UM-303 trial protocol for retifanlimab in anal cancer was one year, clinicians may continue therapy for patients with a partial response. If active, controlled disease remains, the risk of progression upon stopping may outweigh the low toxicity risk from monotherapy, prompting a discussion to continue treatment.