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
956 drug discovery papers about Squamous cell carcinoma of the anal canal, with 3 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
956 drug discovery papers about Squamous cell carcinoma of the anal canal, with 3 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-05 | FDA Approval Summary: Retifanlimab for the treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal.
On May 15, 2025, the Food and Drug Administration approved retifanlimab in combination with carboplatin and paclitaxel for treating unresectable or metastatic squamous cell carcinoma of the anal canal (SCAC), and as a single agent for second-line SCAC treatment. These approvals were based on POD1UM-303 and POD1UM-202 trials. In POD1UM-303, 308 patients with no prior systemic treatment for advanced disease were randomized 1:1 to receive retifanlimab or placebo, both combined with carboplatin and paclitaxel. The primary efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. The trial demonstrated a statistically significant PFS improvement with a hazard ratio (HR) of 0.63 (95% CI: 0.47, 0.84, p-value 0.0006). Median PFS was 9.3 months (95% CI: 7.5, 11.3) and 7.4 months (95% CI: 7.1, 7.7) in the retifanlimab and placebo arms, respectively. Interim OS results were not statistically significant (HR 0.70 [95% CI: 0.49, 1.01]), although the point estimate for OS was 29.2 months (95% CI: 24.2, NE) in the retifanlimab arm and 23 months (95% CI: 15.1, 27.9) for placebo. Second-line approval was based on POD1UM-202, a single-arm trial of 94 patients receiving single-agent retifanlimab. The independent centrally assessed overall response rate was 14% (95% CI: 8, 23). No new adverse safety signals were identified. The approval of retifanlimab as a single agent or in combination with chemotherapy provides a new therapeutic option for patients with unresectable or metastatic SCAC.
2026-07-22 | Durable Cancer Control and Extended Long-Term Survival Following Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal: A Cohort Study.
Salvage surgery is the standard-of-care for patients with squamous cell carcinoma of the anal canal (SCCa) who experience isolated locoregional failure after upfront chemoradiotherapy. While perioperative morbidity and short-term survival outcomes have been described, long-term outcomes of surgical salvage are unknown. This study examines recurrence patterns and survival in a cohort of patients with extended follow-up. A retrospective chart review was performed on a cohort of consecutive patients who underwent salvage surgery at two specialized cancer centers between 1987 and 2006. Overall, disease-specific and re-recurrence-free survival (OS, DSS, RRFS) were estimated using the Kaplan-Meier method. Prognostic variables were evaluated using univariate and multivariable Cox models. Forty patients were included (29 female, 11 male; median age 56). Median follow-up was 16.5 years (IQR 15.0-20.5) for patients alive at last follow-up. Re-recurrence developed in 52% of patients, 95% of which occurred within 3 years of salvage surgery; re-recurrence was associated with a 91% risk of subsequent SCCa-specific mortality. DSS was 45% (95% CI 30-61) at 5 years, after which point conditional 5-year DSS was 100%. Approximately half of patients who undergo salvage surgery for persistent/recurrent SCCa experience durable cancer control with extended long-term survival. Emerging treatment options such as immunotherapy should be evaluated relative to this benchmark.
2026-07-22 | An evaluation of retifanlimab-dlwr with carboplatin and paclitaxel and as a single agent for squamous cell carcinoma of the anal canal.
Anal squamous cell carcinoma (SCC) is a rare cancer. Metastatic anal SCC is still a significant clinical challenge due to limited treatment options and poor outcomes. This review paper will focus on retifanlimab, a humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) pathway, and its role in the treatment of metastatic anal SCC, both as monotherapy or in combination with chemotherapy. This review will evaluate its efficacy, safety, and place within the current therapeutic landscape. The POD1UM-303 trial is the first randomized phase III study for patients with metastatic and locally, advanced unresectable anal SCC. The results from POD1UM-303 are practice-changing, establishing retifanlimab in combination with carboplatin and paclitaxel as a new standard of care for first-line treatment in this setting. Current research includes investigating earlier integration of PD-(L)1 inhibitors with definitive chemoradiotherapy in the locally advanced setting. Further biomarker-driven studies are essential to guide treatment and improve patient selection.
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%)
2026-08-05 | FDA Approval Summary: Retifanlimab for the treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal.
On May 15, 2025, the Food and Drug Administration approved retifanlimab in combination with carboplatin and paclitaxel for treating unresectable or metastatic squamous cell carcinoma of the anal canal (SCAC), and as a single agent for second-line SCAC treatment. These approvals were based on POD1UM-303 and POD1UM-202 trials. In POD1UM-303, 308 patients with no prior systemic treatment for advanced disease were randomized 1:1 to receive retifanlimab or placebo, both combined with carboplatin and paclitaxel. The primary efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. The trial demonstrated a statistically significant PFS improvement with a hazard ratio (HR) of 0.63 (95% CI: 0.47, 0.84, p-value 0.0006). Median PFS was 9.3 months (95% CI: 7.5, 11.3) and 7.4 months (95% CI: 7.1, 7.7) in the retifanlimab and placebo arms, respectively. Interim OS results were not statistically significant (HR 0.70 [95% CI: 0.49, 1.01]), although the point estimate for OS was 29.2 months (95% CI: 24.2, NE) in the retifanlimab arm and 23 months (95% CI: 15.1, 27.9) for placebo. Second-line approval was based on POD1UM-202, a single-arm trial of 94 patients receiving single-agent retifanlimab. The independent centrally assessed overall response rate was 14% (95% CI: 8, 23). No new adverse safety signals were identified. The approval of retifanlimab as a single agent or in combination with chemotherapy provides a new therapeutic option for patients with unresectable or metastatic SCAC.
2026-07-22 | Durable Cancer Control and Extended Long-Term Survival Following Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal: A Cohort Study.
Salvage surgery is the standard-of-care for patients with squamous cell carcinoma of the anal canal (SCCa) who experience isolated locoregional failure after upfront chemoradiotherapy. While perioperative morbidity and short-term survival outcomes have been described, long-term outcomes of surgical salvage are unknown. This study examines recurrence patterns and survival in a cohort of patients with extended follow-up. A retrospective chart review was performed on a cohort of consecutive patients who underwent salvage surgery at two specialized cancer centers between 1987 and 2006. Overall, disease-specific and re-recurrence-free survival (OS, DSS, RRFS) were estimated using the Kaplan-Meier method. Prognostic variables were evaluated using univariate and multivariable Cox models. Forty patients were included (29 female, 11 male; median age 56). Median follow-up was 16.5 years (IQR 15.0-20.5) for patients alive at last follow-up. Re-recurrence developed in 52% of patients, 95% of which occurred within 3 years of salvage surgery; re-recurrence was associated with a 91% risk of subsequent SCCa-specific mortality. DSS was 45% (95% CI 30-61) at 5 years, after which point conditional 5-year DSS was 100%. Approximately half of patients who undergo salvage surgery for persistent/recurrent SCCa experience durable cancer control with extended long-term survival. Emerging treatment options such as immunotherapy should be evaluated relative to this benchmark.
2026-07-22 | An evaluation of retifanlimab-dlwr with carboplatin and paclitaxel and as a single agent for squamous cell carcinoma of the anal canal.
Anal squamous cell carcinoma (SCC) is a rare cancer. Metastatic anal SCC is still a significant clinical challenge due to limited treatment options and poor outcomes. This review paper will focus on retifanlimab, a humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) pathway, and its role in the treatment of metastatic anal SCC, both as monotherapy or in combination with chemotherapy. This review will evaluate its efficacy, safety, and place within the current therapeutic landscape. The POD1UM-303 trial is the first randomized phase III study for patients with metastatic and locally, advanced unresectable anal SCC. The results from POD1UM-303 are practice-changing, establishing retifanlimab in combination with carboplatin and paclitaxel as a new standard of care for first-line treatment in this setting. Current research includes investigating earlier integration of PD-(L)1 inhibitors with definitive chemoradiotherapy in the locally advanced setting. Further biomarker-driven studies are essential to guide treatment and improve patient selection.
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%)
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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 |
|---|---|---|---|---|---|
imiquimod | small molecules | FDA | 2025-12-09 | — | Delnaggar Biotech Group |
5-fluorouracil | 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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