The INTERACT trial showed carboplatin/paclitaxel had similar response rates and PFS to cisplatin/5-FU. It became the standard of care primarily due to its significantly better side effect profile, with lower rates of bone marrow suppression, fatigue, and GI toxicity.
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.
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.
Despite the HPV vaccine's effectiveness against related cancers, population-level incidence of anal cancer is projected to keep increasing. This is likely due to the lag time for vaccination's population-level impact and disparities in vaccine uptake across different socioeconomic and ethnic groups.
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.
The trial allowed patients in the placebo group to receive retifanlimab upon progression (crossover). This common design dilutes the observed overall survival difference. While initial results were not statistically significant, updated data revealed a clinically meaningful 10.6-month median OS improvement.