RARE DISEASE
Squamous cell carcinoma of the anal canal
Squamous cell carcinoma of the anal canal
Squamous cell carcinoma of the anal canal
Drug discovery
4
drugs
With orphan designations
Overview
Squamous cell carcinoma of the anal canal (SCCAC) is a rare, HPV-associated malignancy linked to immunosuppression, smoking, and high-risk sexual behavior. It accounts for ~90% of anal cancers, with rising global incidence (+2–3% annually) and mortality. Treatment focuses on sphincter preservation through chemoradiation (CRT), with 5-fluorouracil/mitomycin C as the standard regimen. While CRT achieves 5-year survival rates of 65–80%, locoregional failure occurs in 20–30% of cases [1][2][6][16].
Burden
U.S. incidence: ~10,540 cases annually (2024); 5-year survival 56.9% in PLWH vs. 66.8% overall [7][14][16].
Stage migration: Distant-stage incidence tripled (AAPC +7.5–8.6%) since 2001; mortality increased 3.1% annually [4][14].
HPV vaccination may reduce future cases but remains underutilized (38.6% U.S. coverage) [12][14].
Therapies
Stage I-III: CRT (Nigro protocol) with 5-FU/mitomycin C and 50–59 Gy radiotherapy; local excision for T1N0 tumors [1][8][13].
Recurrent/metastatic disease: Carboplatin/paclitaxel or cisplatin-based regimens; salvage abdominoperineal resection (77% locoregional control) [6][8].
Emerging: PD-1 inhibitors (e.g., retifanlimab) for refractory cases; de-escalation trials (e.g., DECREASE) to reduce CRT toxicity [6][12][20].
Categories: rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
951 drug discovery papers related to Squamous cell carcinoma of the anal canal, with 3 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
951 drug discovery papers related to Squamous cell carcinoma of the anal canal, with 3 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-05-29 | Updates on Management of Anal Cancer: A New Era Has Begun.
Squamous cell carcinoma of the anal canal (SCAC) is a rare, human papillomavirus-driven malignancy with a rising global incidence and an increasingly dynamic therapeutic landscape. This review summarizes recent advances and current evidence in the management of SCAC, with a focus on immunotherapy, systemic treatment strategies, and optimization of curative-intent approaches. For locally advanced SCAC, concurrent chemoradiotherapy with fluorouracil and mitomycin C remains the standard of care, on the basis of multiple randomized trials demonstrating improved disease control and organ preservation compared with radiotherapy alone. These studies also show that treatment intensification with alternative chemotherapy, induction therapy, or radiation dose escalation does not improve outcomes. Given the curative intent, maintaining quality of life is a key consideration, and current studies are evaluating radiation dose optimization to reduce treatment-related toxicity, as well as the integration of immunotherapy to improve treatment efficacy. In metastatic SCAC, the combination of carboplatin and paclitaxel is the established first-line chemotherapy backbone. The addition of the PD-1 inhibitor retifanlimab to chemotherapy has demonstrated improved clinical outcomes and is now a preferred first-line approach. In the treatment-refractory setting, anti-PD-1 monotherapy provides modest response rates and remains a standard option for immunotherapy-naïve patients. Together, these findings summarize the current evidence base guiding the management of SCAC.
2026-05-28 | Efficacy and safety of retifanlimab across solid tumors: A systematic review and meta-analysis.
e14585 Background: Retifanlimab is a PD-1 inhibitor with demonstrated activity in several solid tumors, including FDA approved indication in squamous cell carcinoma of the anal canal (SCAC). However, its efficacy and safety across tumor types have not been systematically synthesized. Methods: We conducted a systematic review and meta analysis of prospective trials evaluating retifanlimab in solid tumors. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and oncology conferences were searched through January 2026. Pooled ORR and CR were estimated using random effects models. Subgroup analyses were performed by tumor type, treatment line, and regimen. Results: Nineteen studies encompassing 1,113 patients across phase I-III trials were included. Tumor types included SCAC, Merkel cell carcinoma (MCC), NSCLC, HNSCC, sarcoma, and MSI-H endometrial cancer. Pooled ORR was 57.2% (95% CI, 48.6–65.9%; I² = 87%); CR rate was 26.3% (95% CI, 19.7–32.8%). First-line treatment showed significantly higher ORR than later lines (79.8% vs 39.5%). By tumor type, higher ORRs were observed in HNSCC (74.8%), NSCLC (74.7%), MCC (69.4%), and SCAC (65.4%). Safety was consistent with PD-1 inhibitor class: any-grade irAEs in 27.8%, grade ≥3 in 6.3%. Conclusions: Retifanlimab demonstrates clinically meaningful antitumor activity across multiple solid tumors, with greatest benefit in first line treatment. Consistency of efficacy and safety signals supports ongoing development. Pooled ORR by tumor type. Tumor Studies Patients ORR (95% CI) SCAC 3 402 65.4% (40.7–90.2%) MCC 2 111 69.4% (37.2–101.6%) NSCLC 2 58 74.7% (39.1–110.3%) HNSCC 2 50 74.8% (53.3–96.4%) Sarcoma 3 88 37.5% (21.8–53.2%)
2026-05-11 | Real-world outcomes of pembrolizumab in advanced anal cancer: a nationwide Danish anal Cancer Group report.
Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy with limited treatment options for advanced or metastatic disease. Immune checkpoint inhibitors (ICIs) have shown durable responses in clinical trials, but evidence derives from small and highly selected populations. This study investigates the effectiveness and tolerability of pembrolizumab in an unselected real-world cohort. Patient/material and methods: This retrospective, multicenter cohort study evaluated the real-world efficacy, durability, and safety of pembrolizumab in Danish patients with advanced or metastatic SCCA treated between September 2018 and September 2023. A total of 37 patients, who received at least one dose of pembrolizumab for non-resectable, recurrent or metastatic disease, were included (89% ≥ 2nd line). Median age was 64 years, the majority were female (64.9%), and most tumours were human papillomavirus (HPV) (p16) positive (73.0%). The objective response rate (ORR) was 13.5%, with two complete and three partial responses. The clinical benefit rate (CBR) was 48.6%, and two patients had durable responses exceeding 24 months. Median progression-free survival (PFS) and overall survival (OS) were 4.0 months 95% confidence interval (CI) (2.6-5.5) and 12.1 months 95% CI (7.6-15.2), respectively. Patients with good performance status and HPV-positive disease had significantly improved survival outcomes. Treatment was well tolerated, and no treatment-related deaths were reported. In this real-world cohort, pembrolizumab demonstrated durable responses in a subset of patients with advanced SCCA and an acceptable safety profile. Outcomes were comparable to clinical trial data, indicating modest activity. Findings support using pembrolizumab as a treatment option in selected patients, but further evidence is needed to refine its role.
2026-05-29 | Updates on Management of Anal Cancer: A New Era Has Begun.
Squamous cell carcinoma of the anal canal (SCAC) is a rare, human papillomavirus-driven malignancy with a rising global incidence and an increasingly dynamic therapeutic landscape. This review summarizes recent advances and current evidence in the management of SCAC, with a focus on immunotherapy, systemic treatment strategies, and optimization of curative-intent approaches. For locally advanced SCAC, concurrent chemoradiotherapy with fluorouracil and mitomycin C remains the standard of care, on the basis of multiple randomized trials demonstrating improved disease control and organ preservation compared with radiotherapy alone. These studies also show that treatment intensification with alternative chemotherapy, induction therapy, or radiation dose escalation does not improve outcomes. Given the curative intent, maintaining quality of life is a key consideration, and current studies are evaluating radiation dose optimization to reduce treatment-related toxicity, as well as the integration of immunotherapy to improve treatment efficacy. In metastatic SCAC, the combination of carboplatin and paclitaxel is the established first-line chemotherapy backbone. The addition of the PD-1 inhibitor retifanlimab to chemotherapy has demonstrated improved clinical outcomes and is now a preferred first-line approach. In the treatment-refractory setting, anti-PD-1 monotherapy provides modest response rates and remains a standard option for immunotherapy-naïve patients. Together, these findings summarize the current evidence base guiding the management of SCAC.
2026-05-28 | Efficacy and safety of retifanlimab across solid tumors: A systematic review and meta-analysis.
e14585 Background: Retifanlimab is a PD-1 inhibitor with demonstrated activity in several solid tumors, including FDA approved indication in squamous cell carcinoma of the anal canal (SCAC). However, its efficacy and safety across tumor types have not been systematically synthesized. Methods: We conducted a systematic review and meta analysis of prospective trials evaluating retifanlimab in solid tumors. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and oncology conferences were searched through January 2026. Pooled ORR and CR were estimated using random effects models. Subgroup analyses were performed by tumor type, treatment line, and regimen. Results: Nineteen studies encompassing 1,113 patients across phase I-III trials were included. Tumor types included SCAC, Merkel cell carcinoma (MCC), NSCLC, HNSCC, sarcoma, and MSI-H endometrial cancer. Pooled ORR was 57.2% (95% CI, 48.6–65.9%; I² = 87%); CR rate was 26.3% (95% CI, 19.7–32.8%). First-line treatment showed significantly higher ORR than later lines (79.8% vs 39.5%). By tumor type, higher ORRs were observed in HNSCC (74.8%), NSCLC (74.7%), MCC (69.4%), and SCAC (65.4%). Safety was consistent with PD-1 inhibitor class: any-grade irAEs in 27.8%, grade ≥3 in 6.3%. Conclusions: Retifanlimab demonstrates clinically meaningful antitumor activity across multiple solid tumors, with greatest benefit in first line treatment. Consistency of efficacy and safety signals supports ongoing development. Pooled ORR by tumor type. Tumor Studies Patients ORR (95% CI) SCAC 3 402 65.4% (40.7–90.2%) MCC 2 111 69.4% (37.2–101.6%) NSCLC 2 58 74.7% (39.1–110.3%) HNSCC 2 50 74.8% (53.3–96.4%) Sarcoma 3 88 37.5% (21.8–53.2%)
2026-05-11 | Real-world outcomes of pembrolizumab in advanced anal cancer: a nationwide Danish anal Cancer Group report.
Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy with limited treatment options for advanced or metastatic disease. Immune checkpoint inhibitors (ICIs) have shown durable responses in clinical trials, but evidence derives from small and highly selected populations. This study investigates the effectiveness and tolerability of pembrolizumab in an unselected real-world cohort. Patient/material and methods: This retrospective, multicenter cohort study evaluated the real-world efficacy, durability, and safety of pembrolizumab in Danish patients with advanced or metastatic SCCA treated between September 2018 and September 2023. A total of 37 patients, who received at least one dose of pembrolizumab for non-resectable, recurrent or metastatic disease, were included (89% ≥ 2nd line). Median age was 64 years, the majority were female (64.9%), and most tumours were human papillomavirus (HPV) (p16) positive (73.0%). The objective response rate (ORR) was 13.5%, with two complete and three partial responses. The clinical benefit rate (CBR) was 48.6%, and two patients had durable responses exceeding 24 months. Median progression-free survival (PFS) and overall survival (OS) were 4.0 months 95% confidence interval (CI) (2.6-5.5) and 12.1 months 95% CI (7.6-15.2), respectively. Patients with good performance status and HPV-positive disease had significantly improved survival outcomes. Treatment was well tolerated, and no treatment-related deaths were reported. In this real-world cohort, pembrolizumab demonstrated durable responses in a subset of patients with advanced SCCA and an acceptable safety profile. Outcomes were comparable to clinical trial data, indicating modest activity. Findings support using pembrolizumab as a treatment option in selected patients, but further evidence is needed to refine its role.
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Drug Discovery Landscape
4 orphan drug designations for Squamous cell carcinoma of the anal canal.
4 orphan drug designations for Squamous cell carcinoma of the anal canal.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
5-fluorouracil | small molecules | FDA | 2025-12-09 | — | Delnaggar Biotech Group |
imiquimod | small molecules | FDA | 2025-12-09 | — | Delnaggar Biotech Group |
Cisplatin | small molecules | FDA | 2016-09-06 | — | Privo Technologies |
ADXS11-001 | proteins | FDA | 2013-08-12 | — | Advaxis, Inc. |
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