# Clinicopathologic Features Associated with Survival for Immune Checkpoint Blockade in Patients with Metastatic Anal Cancer

## TL;DR

This study finds that patients with metastatic anal cancer who have only lymph node spread may benefit more from immunotherapy, showing longer survival compared to those with spread to other organs.

## Contribution

The study identifies lymph node-only metastases as a potential biomarker for better immunotherapy outcomes in metastatic anal cancer.

## Key findings

- Patients with lymph node-only metastases had significantly longer progression-free survival with immunotherapy (11.3 months) compared to those with visceral involvement (3.1 months).
- Median progression-free survival for first-, second-, and third-line therapies was 7.2, 3.7, and 4.7 months respectively, showing declining effectiveness with each treatment line.
- Immunotherapy and chemotherapy showed similar progression-free survival in treatment-refractory settings (3.6 vs. 4.4 months).

## Abstract

In addition to cytotoxic chemotherapy, strategies for the treatment of metastatic anal cancer have evolved to include immune checkpoint inhibitors. However, biomarkers that can predict immunotherapy treatment outcomes are limited and the aim of this study is to identify patient- and disease-related characteristics that predict outcomes of immunotherapy in the treatment of metastatic anal cancer. This retrospective study analyzed 105 patients with unresectable or metastatic anal cancer, using Kaplan–Meier analyses to assess progression-free and overall survival across sequential lines of treatment. These findings highlight one of the first analyses to characterize progression-free survival across treatment lines for metastatic anal cancer, showing that the metastatic pattern can influence response to immunotherapy. Lymph node-only metastases were identified as a potential positive predictive factor for favorable outcomes, but this research also points out the need for future trials that can refine personalized strategies for the treatment of metastatic anal cancer.

Background/Objectives: Anal cancer is a rare malignancy with limited treatment options. Immune checkpoint inhibitors have shown benefits in some patients with metastatic disease, but predictive factors for immunotherapy response remain undefined. This study retrospectively evaluated clinical and pathological features associated with survival outcomes in metastatic anal cancer treated with immunotherapy. Methods: Data from 105 patients with metastatic anal cancer were analyzed. Kaplan–Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS), with subgroup comparisons utilizing the Mantel–Cox test. Associations between survival and clinicopathologic features were assessed with Fisher’s exact test. Results: Of the patients, 69 (65.7%) received immunotherapy during the first three treatment lines. With a median follow-up of 23.2 months, the median PFS for first-, second-, and third-line systemic therapies was 7.2, 3.7, and 4.7 months, respectively (χ2 = 14.2; p < 0.001). In the treatment-refractory setting, median PFS was similar for immunotherapy and chemotherapy: 3.6 months (95% CI, 2.3–4.9) vs. 4.4 months (95% CI, 3.8–5.0), respectively (HR 0.89, 95% CI 0.60–1.3; p = 0.52). Among patients treated with immunotherapy, patients with lymph node-only metastases had significantly prolonged PFS compared to patients with visceral organ involvement (11.3 vs. 3.1 months; HR 0.49, 95% CI 0.21–0.74; p = 0.03). Conclusions: Patients with lymph node-only metastatic anal cancer experienced significantly prolonged PFS with immunotherapy relative to those with involvement of other distant organs, highlighting a distinct subgroup of patients who may benefit from immunotherapy. We also contextualize PFS outcomes across treatment lines for metastatic anal cancer, which can be applied towards the design of future immunotherapy clinical trials.