Senthil Kumar: Comprehensive Overview of First-Line Treatment for Metastatic Anal Cancer

Senthil Kumar, Medical Oncologist at Red Hills, Chennai shared a post on X:

“Comprehensive Overview of First-Line Treatment for Metastatic Anal Cancer.

1. InterAACT Trial

Arms: Cisplatin plus 5-fluorouracil (5-FU) vs. carboplatin plus weekly paclitaxel.

Carboplatin/Paclitaxel:

Progression-Free Survival (PFS):
8.1 months.

Overall Survival (OS):
20 months.

Cisplatin/5-FU (Comparator Arm):

Progression-Free Survival (PFS):
5.7 months.

Overall Survival (OS):
12.3 months.

2. FOLFCIS Regimen

Progression-Free Survival (PFS):
7.1 months.

Overall Survival (OS):
22.1 months.

3. DCF (Docetaxel, Cisplatin, and 5-Fluorouracil) Regimen

Efficacy:

Progression-Free Survival (PFS):
11 months.

Toxicity:

Grade 3 or Higher Adverse Effects: 83% in the DCF regimen.

Patient Selection:

Best suited for younger, fit patients (Performance Status 0), particularly in high-volume disease, oligometastatic cases, or when rapid response is critical.

Significant toxicity limits its use to selected cases.

4. Modified DCF

Progression-Free Survival (PFS):
11 months.

Toxicity:

Grade 3 + Adverse Effects: 53%, lower than the standard DCF regimen.

Patient Selection:

A viable option for slightly less fit or elderly patients (Performance Status 1).

5. Cisplatin/5-Fluorouracil (Cis 5-FU)

Progression-Free Survival (PFS):
5.7 months (as per InterAACT trial).

Overall Survival (OS):
12.3 months.

Objective Response Rate (ORR): noted to be high ( 60-75%), but responses were often not sustained.

6. FOLFOX Regimen

Efficacy: Limited data in metastatic anal cancer; more commonly used in colorectal cancers.

Role of Immunotherapy

7. POD1UM-303/InterAACT 2 Trial

Arms: Retifanlimab (anti-PD-1) combined with standard chemotherapy (carboplatin and paclitaxel) vs. chemotherapy alone.

Efficacy:

Progression-Free Survival (PFS):

Median PFS was 9.3 months in the combination arm compared to 7.4 months in the chemotherapy-alone arm (HR 0.63; p=0.0006).

Overall Survival (OS):

A trend toward improved OS was observed with the combination therapy (29.2 months vs. 23.0 months; HR 0.70; p=0.0273).

Significance:

This trial represents the largest randomized study in metastatic unresectable anal cancer, indicating that adding retifanlimab to chemotherapy may become a new standard of care.

8. SCARCE-PRODIGE 60 Trial

Study Type: Phase II study.

Arms: DCF with or without atezolizumab as first-line treatment in anal cancer.

Efficacy:

12-Month Progression-Free Survival (PFS): 44.2% in the experimental arm.

Objective Response Rate (ORR): 74.6% in the experimental arm.

Grade 3 Toxicities: 59.0% in the experimental arm.

Outcome – negative trial.

Final Insights

The best regimen for first-line treatment of metastatic anal cancer remains carboplatin plus weekly paclitaxel, as demonstrated by the InterAACT trial.

Other acceptable regimens include:

Next best option: FOLFCIS, particularly in cases where carboplatin/paclitaxel is not feasible.

DCF: Recommended for young, fit patients with high-volume disease, oligometastases, or when a rapid response is required. However, the significant toxicity profile (83% Grade 3+) limits its use to carefully selected cases.

Modified DCF: Suitable for slightly less fit or elderly patients, offering comparable efficacy with reduced toxicity (53% Grade 3+).

Cisplatin/5-FU: Shows a high objective response rate (ORR), but responses are often not sustained, making it less favorable compared to other regimens.

FOLFOX: A reasonable alternative with limited supporting data.

New Emerging Standard of Care: The POD1UM-303 combination of retifanlimab with carboplatin and paclitaxel is showing promising data and may redefine the standard of care in the near future.

HIV and HPV Status: Currently, these factors do not influence treatment strategies, as evidence does not indicate differential outcomes based on these statuses.”