From the Guidelines
For second-line treatment of metastatic anal cancer, immunotherapy is generally preferred over capecitabine plus oxaliplatin. The most recent evidence from the 2023 NCCN clinical practice guidelines in oncology 1 supports the use of PD-1 inhibitors like nivolumab or pembrolizumab, which have shown response rates of 15-24% and are associated with more durable responses.
Key Points to Consider
- PD-1 inhibitors like nivolumab (240 mg IV every 2 weeks) or pembrolizumab (200 mg IV every 3 weeks) have been added as preferred options for patients with metastatic anal cancer who have experienced progression on first-line chemotherapy.
- These immunotherapies work by enhancing the body's immune response against cancer cells by blocking the PD-1 pathway that tumors use to evade immune detection.
- Capecitabine plus oxaliplatin can be considered for patients who cannot receive immunotherapy due to contraindications such as severe autoimmune disorders or organ transplantation.
- The decision should be individualized based on patient factors including performance status, comorbidities, and prior treatment response.
- Immunotherapy typically has a more favorable toxicity profile compared to chemotherapy, with immune-related adverse events being the primary concern rather than the myelosuppression, neuropathy, and gastrointestinal toxicity commonly seen with capecitabine-oxaliplatin.
- Regular monitoring for immune-related adverse events is essential when using immunotherapy, as seen in the KEYNOTE-028 trial and the phase II KEYNOTE-158 study 1.
Patient Selection
- Microsatellite instability/mismatch repair testing is not required for patient selection, as microsatellite instability is uncommon in anal cancer 1.
- Patients with PD-L1-positive disease may have a higher response rate to pembrolizumab, but this should not be the sole factor in deciding treatment 1.
From the Research
Treatment Options for Metastatic Anal Cancer
- Immunotherapy has shown promise in the treatment of metastatic anal cancer, with studies demonstrating its effectiveness in extending progression-free survival and overall survival 2, 3.
- Nivolumab and pembrolizumab are two immunotherapy options that have been shown to be effective in the treatment of metastatic anal cancer, with response rates of 24% and durable clinical responses 2, 3.
- Capecitabine and oxaliplatin are also used in the treatment of metastatic anal cancer, although there is limited evidence comparing their effectiveness to immunotherapy 4, 5.
Comparison of Immunotherapy and Chemotherapy
- A study published in 2017 demonstrated the effectiveness of nivolumab in the treatment of metastatic anal cancer, with a response rate of 24% and a tolerable side effect profile 2.
- Another study published in 2020 highlighted the role of immunotherapy in the treatment of metastatic anal cancer, with nivolumab and pembrolizumab being recommended as second-line treatments 3.
- Chemotherapy regimens such as paclitaxel, ifosfamide, and cisplatin have also been used in the treatment of metastatic anal cancer, although their effectiveness compared to immunotherapy is unclear 4, 5.
Future Directions
- Ongoing research is focused on investigating the use of immunotherapy in combination with other treatments, such as chemotherapy and radiation therapy, to improve outcomes for patients with metastatic anal cancer 5, 6.
- Novel approaches such as T-cell adoptive therapy, HPV-therapeutic vaccines, and bifunctional antibodies combined with HPV vaccines are also being explored in early-stage trials 5, 6.