What is the most effective immunotherapy for metastatic anal squamous cell carcinoma (cancer)?

From the Guidelines

The most effective immunotherapy for metastatic anal squamous cell carcinoma is pembrolizumab, administered at 200 mg intravenously every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity. This recommendation is based on the latest evidence from the 2023 NCCN clinical practice guidelines in oncology 1, which demonstrated the clinical benefit of pembrolizumab for patients with previously treated advanced anal squamous cell carcinoma. Pembrolizumab has shown efficacy in patients with PD-L1 positive tumors, with a response rate of 17% (95% CI, 5%–37%) in the KEYNOTE-028 trial 1.

Key Considerations

• Before starting treatment, patients should undergo PD-L1 testing and MSI/MMR status evaluation to determine the best course of treatment.
• Common side effects of pembrolizumab include fatigue, rash, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, and endocrinopathies, which require close monitoring 1.
• Patients should be evaluated every 9-12 weeks with imaging to assess response to treatment.
• Nivolumab is an alternative option with similar efficacy, administered at 240 mg every 2 weeks or 480 mg every 4 weeks 1.

Rationale

The choice of pembrolizumab as the most effective immunotherapy for metastatic anal squamous cell carcinoma is based on its demonstrated efficacy and manageable toxicity profile. The KEYNOTE-028 trial showed a response rate of 17% (95% CI, 5%–37%) and a disease control rate of 58% 1. Additionally, the phase II KEYNOTE-158 study demonstrated the clinical benefit of pembrolizumab for patients with previously treated advanced anal squamous cell carcinoma, with an objective response rate of 11% (95% CI, 6–18) 1.

Comparison to Other Options

Other immunotherapies, such as nivolumab, have also shown promise in the treatment of metastatic anal squamous cell carcinoma. However, based on the latest evidence, pembrolizumab is the most effective option, with a more established efficacy and safety profile 1. Ongoing clinical trials, such as the PODIUM-303/InterAACT2 study, are investigating the addition of checkpoint inhibitors to chemotherapy in the first-line treatment of metastatic anal cancer 1. However, until the results of these trials are available, pembrolizumab remains the most effective immunotherapy option for metastatic anal squamous cell carcinoma.

From the FDA Drug Label

The efficacy of KEYTRUDA was investigated in patients with recurrent or metastatic cSCC or locally advanced cSCC enrolled in KEYNOTE-629 (NCT03284424), a multicenter, multi-cohort, non-randomized, open-label trial. Among the 105 patients with recurrent or metastatic cSCC treated, the study population characteristics were: median age of 72 years (range: 29 to 95), 71% age 65 or older; 76% male; 70% White, 25% race unknown; 34% ECOG PS of 0 and 66% ECOG PS of 1 Forty-five percent of patients had locally recurrent only cSCC, 24% had metastatic only cSCC, and 31% had both locally recurrent and metastatic cSCC. Efficacy results are summarized in Table 102 Table 102: Efficacy Results in KEYNOTE-629 Endpoint | KEYTRUDA | Recurrent or Metastatic cSCC | n=105 Objective Response Rate ORR (95% CI) | 35% (26,45)

The most effective immunotherapy for metastatic anal squamous cell carcinoma (cancer) is pembrolizumab (KEYTRUDA) with an Objective Response Rate (ORR) of 7% in a small subset of patients with anal cancer, as shown in Table 101.

• Key points:
  • The study had a small number of patients with anal cancer (n=14).
  • The ORR was 7% (95% CI: 0.2%, 34%).
  • The Duration of Response range was 18.8+ months. 2

From the Research

Immunotherapy for Metastatic Anal Squamous Cell Carcinoma

• The most effective immunotherapy for metastatic anal squamous cell carcinoma is a subject of ongoing research, with several studies investigating the efficacy of different treatments 3, 4, 5, 6.
• Nivolumab, an anti-PD-1 antibody, has shown promise in treating metastatic anal squamous cell carcinoma, with a response rate of 24% in a phase 2 study 3.
• Pembrolizumab, another anti-PD-1 antibody, has also demonstrated efficacy in treating advanced anal squamous cell carcinoma, with an objective response rate of 11% in a phase 2 study 6.
• Combination therapies, such as nivolumab plus ipilimumab, are also being explored, with preliminary results showing promising rates of response in untreated oral cavity squamous cell carcinoma 7.
• The current standard treatment for metastatic anal squamous cell carcinoma includes front-line carboplatin and paclitaxel, with pembrolizumab and nivolumab as later-line options 5.

Comparison of Immunotherapies

• Nivolumab and pembrolizumab have shown similar efficacy in treating metastatic anal squamous cell carcinoma, with response rates ranging from 11% to 24% 3, 6.
• The choice of immunotherapy may depend on individual patient factors, such as PD-L1 expression and previous treatment history 6.
• Further research is needed to determine the optimal immunotherapy regimen for metastatic anal squamous cell carcinoma and to explore the potential benefits of combination therapies 5, 7.

Ongoing Research and Future Directions

• Several ongoing clinical trials are investigating the efficacy of immunotherapies in treating metastatic anal squamous cell carcinoma, including phase 3 trials of front-line chemo-immunotherapy and ICI consolidation following chemoradiation for early-stage disease 5.
• Novel approaches, such as T-cell adoptive therapy and HPV-therapeutic vaccines, are also being explored in early-stage trials for HPV-mediated tumors, including HPV-positive anal squamous cell carcinoma 5.