Retifanlimab Plus Chemotherapy Extends Survival in Advanced Anal Cancer

The addition of retifanlimab to carboplatin-paclitaxel chemotherapy improved overall survival (OS) in patients with advanced squamous cell carcinoma of the anal canal, according to final findings from the phase 3 POD1UM-303/InterAACT-2 study published in Annals of Oncology.

For oncology nurses caring for patients with metastatic anal cancer, the findings may signal a shift in frontline management for a rare disease with historically poor outcomes and limited treatment advancements. Investigators reported that retifanlimab plus chemotherapy demonstrated clinically meaningful survival improvement while maintaining a manageable and predictable safety profile.

Patients treated with retifanlimab plus carboplatin-paclitaxel achieved a median OS of 32.8 months compared with 22.2 months among those treated with placebo plus chemotherapy (HR, 0.75; 95% CI, 0.55-1.01; P = .0305).

Researchers also confirmed continued progression-free survival (PFS) benefit with the immunotherapy combination. Previous analyses showed a median PFS of 9.3 months with retifanlimab plus chemotherapy versus 7.4 months with chemotherapy alone (HR, 0.63; 95% CI, 0.47-0.84; P = .0006).

What oncology nurses should know about the efficacy findings

The study demonstrated improved tumor response and disease control outcomes with the addition of retifanlimab. The overall response rate (ORR) was 56.5% in the retifanlimab arm compared with 44.8% in the placebo arm. Disease control rates were 87.7% and 80.5%, respectively.

Investigators noted that the survival benefit widened over time. Interim analyses had shown a 6-month OS difference between treatment groups, while the final analysis demonstrated a 10.6-month median OS improvement favoring retifanlimab plus chemotherapy.

For nurses involved in patient education, these findings may help guide conversations surrounding treatment expectations, disease control and the potential role of immunotherapy in frontline metastatic anal cancer care.

The OS benefit was consistent across all analyzed subgroups. Additionally, crossover-adjusted analyses supported the durability of the findings despite 77 patients in the placebo arm later crossing over to receive retifanlimab monotherapy after progression. Investigators reported that crossover had a substantial impact on OS outcomes.

Trial details and relevance to nursing practice

POD1UM-303/InterAACT-2 was a randomized, double-blind, multicenter phase 3 study conducted across Europe, Australia, Japan, the United Kingdom and the United States.

The trial enrolled 308 patients with locally advanced or metastatic squamous cell carcinoma of the anal canal who had not received prior systemic therapy. Patients were randomly assigned to receive either retifanlimab plus carboplatin-paclitaxel or placebo plus carboplatin-paclitaxel, with 154 patients in each treatment group.

The primary endpoint was PFS, while OS served as a key secondary endpoint. Additional endpoints included response, safety and exploratory subgroup analyses.

Researchers emphasized the unmet need in this disease setting. Squamous cell carcinoma accounts for approximately 85% to 95% of anal cancer cases and patients with metastatic disease have a reported 5-year relative survival rate of 36%.

The authors also highlighted the association between anal cancer and human papillomavirus (HPV) infection, noting HPV as the primary risk factor.

For oncology nurses, awareness of the increasing incidence of anal cancer and the expanding use of immunotherapy may become increasingly important for symptom management, treatment coordination and patient counseling throughout the continuum of care.

Safety findings and monitoring considerations

Investigators reported that retifanlimab plus carboplatin-paclitaxel was generally well tolerated, with a safety profile that remained predictable and manageable throughout longer follow-up.

Importantly for oncology nursing teams monitoring patients during treatment, no new safety signals or trends emerged during the final OS analysis.

The study authors also reported that post-progression treatment patterns were similar between treatment groups and sensitivity analyses showed no impact of subsequent therapies on OS outcomes.

Researchers acknowledged that OS was a secondary endpoint, making the study underpowered at approximately 70% because of the relatively small patient population enrolled. They also cited challenges associated with conducting adequately powered trials in rare cancers such as anal cancer.

According to the investigators, POD1UM-303/InterAACT-2 is currently the only randomized phase 3 trial demonstrating an OS benefit with chemoimmunotherapy compared with chemotherapy alone in advanced squamous cell carcinoma of the anal canal.

References

Rao S, Samalin-Scalzi E, Evesque L, et al. Survival outcomes in POD1UM-303/InterAACT-2: a phase 3 study of retifanlimab plus carboplatin-paclitaxel in first-line advanced squamous anal cancer. Annals of Oncology. Published online May 5, 2026. doi:10.1016/j.annonc.2026.04.016.