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.

A significant challenge in assessing complete response after neoadjuvant immunotherapy for rectal cancer is the presence of mucin pools. These imaging abnormalities can persist for up to two years, mimicking residual tumor and complicating decisions about non-operative management.

An advisory panel split 50/50 on a two-year immunotherapy regimen but voted 7-to-1 for a one-year drug with similar efficacy. This reveals that for adjuvant therapies in non-metastatic cancer, halving the treatment duration and toxicity exposure can decisively shift the risk/benefit calculation in favor of approval.

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.

Data from the Checkmate 743 trial shows that patients who stopped dual immunotherapy (Nivo/Ipi) due to toxicity can still achieve long-term benefits. A third of these patients had an ongoing response at three years, despite stopping treatment after only four months on average, providing confidence in the regimen.

The next frontier in CSCC isn't just about new drugs, but about optimizing existing ones. A key research area is determining the minimum number of immunotherapy doses required for an optimal response—potentially just one or two—to limit toxicity, reduce treatment burden, and personalize care for high-risk patients.

A PD-L1 CPS score of zero should not automatically disqualify patients with metastatic anal cancer from receiving immunotherapy. The clinical distinction between a CPS of zero and one is marginal, and given the therapy's potential for benefit and low toxicity, clinicians should give patients the benefit of the doubt and offer the treatment.

After immunotherapy, many colorectal cancer patients have residual nodules on scans that appear to be partial responses. However, ctDNA testing can confirm these are often just scar tissue, not active disease. This provides the confidence to stop therapy at the two-year mark and avoid unnecessary surgeries for what are effectively complete responses.

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.