Zynyz Plus Chemotherapy Improves Survival In Advanced Anal Cancer

Final overall survival analysis showed that patients treated with Zynyz (retifanlimab) plus carboplatin-paclitaxel chemotherapy lived a median of 32.8 months compared with 22.2 months for patients who received placebo plus chemotherapy. Researchers described the improvement as clinically meaningful for patients with this difficult-to-treat cancer.

The study also confirmed earlier findings showing that the addition of Zynyz delayed disease progression. Previous analyses reported a median progression-free survival of 9.3 months in the Zynyz group versus 7.4 months in the placebo group.

Researchers also reported that more patients responded to treatment when Zynyz was added to chemotherapy. The overall response rate was 56.5% with the Zynyz combination compared with 44.8% with chemotherapy alone. Disease control rates were 87.7% versus 80.5%.

According to the study authors, the difference in survival between the two groups increased over time. Earlier analyses had shown a six-month improvement in median overall survival, while the final analysis showed a 10.6-month difference favoring the Zynyz combination.

Researchers said the overall survival benefit remained consistent across all patient subgroups evaluated in the study.

What patients should know about advanced anal cancer

Squamous cell carcinoma of the anal canal is the most common type of anal cancer, accounting for approximately 85% to 95% of all cases. Although anal cancer is considered rare, researchers noted that rates are increasing in many countries.

The authors explained that patients with metastatic disease continue to face poor outcomes despite initial responses to platinum-based chemotherapy. They reported that the five-year relative survival rate for patients with metastatic disease is 36%, highlighting the need for new treatment options.

Researchers also noted that human papillomavirus, or HPV, infection is the main risk factor associated with anal cancer.

Zynyz is an immunotherapy designed to help the immune system recognize and attack cancer cells. The treatment had previously shown antitumor activity in cervical cancer and platinum-refractory squamous cell carcinoma of the anal canal in the phase 2 POD1UM-202 study, leading researchers to further evaluate it in POD1UM-303/InterAACT-2.

Trial details for POD1UM-303/InterAACT-2

POD1UM-303/InterAACT-2 was a randomized, double-blind, controlled 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 Zynyz plus carboplatin-paclitaxel chemotherapy or placebo plus carboplatin-paclitaxel chemotherapy. Each treatment group included 154 patients.

The primary goal of the study was progression-free survival, while overall survival served as a key secondary endpoint. Researchers also evaluated response rates, safety and exploratory subgroup analyses.

Seventy-seven patients initially assigned to the placebo plus chemotherapy group later crossed over to receive Zynyz monotherapy after their disease progressed. Researchers said crossover-adjusted analyses continued to support the survival benefit seen with Zynyz plus chemotherapy.

The authors stated that POD1UM-303/InterAACT-2 is the only randomized phase 3 study to demonstrate an overall survival benefit with chemoimmunotherapy compared with chemotherapy alone in patients with advanced squamous cell carcinoma of the anal canal.

Safety findings with Zynyz

Researchers reported that treatment with Zynyz plus carboplatin-paclitaxel was generally well tolerated. The safety profile remained predictable and manageable and was consistent with findings reported during the primary analysis.

Importantly for patients and caregivers, investigators reported that no new safety signals or trends emerged during the longer follow-up period used for the final overall survival analysis.

The study authors also noted that the timing and types of treatments patients received after disease progression were similar between groups and did not appear to affect the overall survival findings.

Researchers acknowledged that one limitation of the study was that overall survival was a secondary endpoint, meaning the study was underpowered at approximately 70% because of the relatively small number of patients enrolled. They also noted the challenges associated with conducting large studies in rare cancers such as anal cancer.

References

1. “Survival outcomes in POD1UM-303/InterAACT-2: a phase 3 study of retifanlimab plus carboplatin–paclitaxel in first-line advanced squamous anal cancer” by Dr. Sheela Rao, et al., Annals of Oncology.

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