Table 1.
FDA-approved locally delivered immunotherapies76
| Locally administered or delivered immunotherapy and FDA approval date | FDA indication and route of administration | Category of agent | Study endpoint(s) supporting approval |
| Efudex (Fluorouracil)*77
1970 |
“… treatment of multiple actinic or solar keratoses. In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites.” Topical solution, 2% or 5% |
5-fluoro-2,4 (1H,3H)-pyrimidinedione | At 1 year after treatment, 39 of 198 patients treated with fluorouracil cream (two times per day for 4 weeks) had tumor residue or recurrence; 80.1% (95% CI 74.7% to 85.9%) of these patients were tumor-free at 3-month and 12-month follow-up.78–80 |
| BCG 1990 |
Treatment and prophylaxis of CIS of the bladder urothelium, and for the prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following TUR. Not recommended for stage TaG1 papillary tumors, unless they are judged to be at high risk of tumor recurrence.† Intravesical instillation |
Attenuated strain of Mycobacterium bovis | Recurrence rate for patients with a history of recurrent superficial TCC of the bladder: 0% (BCG group) vs 40% (thio-tepa group)81
For Patients with Ta/T1 tumors without CIS:
For patients with CIS:
|
| Imiquimod 2004 |
Biopsy-confirmed, primary superficial basal cell carcinoma in adults with normal immune systems.¶ 5% cream, topical application |
TLR-7/8 agonist | Histological clearance rates:
|
| T-VEC October 27, 2015 |
Treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Intratumoral injections into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound |
Genetically modified attenuated HSV-1 oncolytic virus | DRR**: 16.3% (intralesional T-VEC) vs 2.1% (subcutaneous GM-CSF)1 |
| Nadofaragene firadenovec-vncg December 16, 2022 |
High-risk BCG unresponsive NMIBC with CIS with or without papillary tumors.†† Intravesical instillation |
Non-replicating adenoviral vector-based gene therapy | CR‡‡: 51% (95% CI 41% to 61%) DOR: 9.7 months (range 3 to 52+)83 |
*Although 5-FU is a chemotherapy, not an immunotherapy per se, it can act as an immune modulator84 85 and intratumoral chemotherapy efficacy relies on the immune system.86–88
†Per AUA/SUO and SITC, induction and 1 year or 3 years of maintenance therapy should be considered for intermediate-risk disease and high-risk disease, respectively.89 90
‡Time to treatment failure was defined as termination of treatment due to persistence, recurrence, or progression of disease.
§Complete-response probability estimates were defined as the estimated probability of documented disappearance of disease.
¶Imiquimod is also FDA approved for other non-cancerous skin conditions,91 with off-label uses for melanoma in situ (lentigo maligna type), early-stage mycosis fungoides, and penile cancer (Tis or Ta disease).92
**DRR was defined as an objective response lasting continuously ≥6 months.
††CR was defined as negative cystoscopy with applicable TURBT and biopsies and urine cytology.
‡‡Approval based on a single-arm study.
AUA, American Urological Association; BCG, Bacillus Calmette–Guérin; CI, confidence interval; CIS, carcinoma in situ; CR, complete response rate; DOR, median duration of response; DRR, durable response rate; FDA, Food and Drug Administration; FU, fluorouracil; 5-FU, 5-fluorouracil; GM-CSF, Granulocyte-macrophage colony-stimulating factor; HSV-1, herpes simplex virus-1; NMIBC, non-muscle invasive bladder cancer; SITC, Society for Immunotherapy of Cancer; SUO, Society of Urologic Oncology; TCC, transitional cell carcinoma; TLR, toll-like receptor; TUR, transurethral resection; TURBT, transurethral resection of bladder tumor; T-VEC, talimogene laherparepvec.