Albumin-bound paclitaxel, cisplatin, and bleomycin combination with tislelizumab for stage IV squamous cell carcinoma of the penis without surgical indications: A single-arm, single-center prospective phase II clinical study.
Authors: Shan Xingli , Bai Hongsong , Xie Chengming , Chen Yonghai , Xing Nianzeng , Hu Linjun 
Published: June 2024

5044 Background: In recent years, preclinical studies of the penile cancer microenvironment have shown the presence of a relatively dense immune cell infiltrate and high PD-L1 expression. Here, we present findings to explore the efficacy and safety of albumin-bound paclitaxel, cisplatin and bleomycin combined Tislelizumab regimen for stage IV penile squamous cell carcinoma without surgical indication. Methods: Prospective inclusion of patients with stage IV squamous cell carcinoma of the penis without indications of surgery who are not received chemotherapy or immune checkpoint inhibitors. Patients were treated with chemotherapy combined with Tislelizumab for 4-6 cycles, sequential immunotherapy is permitted for patients who have responded well to local therapy (surgery +/- radiotherapy) . Positive expression of PD-L1 was defined as TPS≥5%. The primary endpoint was ORR, the secondary endpoint was PFS、OS and Safety. Results: 28 patients with stage IV penile squamous cell carcinoma (22 cases with regional lymph node metastasis、6 cases with distant metastasis and 11 cases of local ulceration) were treated with albumin-bound paclitaxel, cisplatin and bleomycin combination with Tislelizumab. The median age of the patients was 56 years (range 38-74 years ), the median chemotherapy cycle was 4 cycles (2-6 cycles), the median immunotherapy cycle was 4 cycles (1-9 cycles), and the median follow-up was 10.4 months. 1 patient (3.5%) were evaluated as CR, 22 patients (78.5%) were evaluated as PR, and 3 patients (10.5%) were evaluated as SD. The ORR was 82.0%. It was significantly higher than the 50% ORR of chemotherapy alone reported in the previous literature. The median PFS was 13.7 months, and The median OS is not arrived. Among the 22 patients with regional lymph node metastasis, 12 patients (54.5%) received surgery or radiotherapy due to good treatment effects. PD-L1 expression was positive in 16 cases (57.1%). 1 case (3.6%) was HPV positive. In adverse event: The incidence of grade 3-4 adverse reactions was 32.1%. 4 cases (32.1%) had grade 3-4 rash with pruritus, 3 cases (10.7%) had grade 3-4 myelosuppression, 1 case (3.6%) had grade 3 pneumonia, 1 case (3.6%) had grade 3 fatigue, and 1 case( 3.6%) had grade 3 alopecia. All adverse reactions resolved after treatment. 2 case (3.6%) stopped immunotherapy due to grade 4 rash with immune pneumonia, and no treatment-related death occurred. Conclusions: Stage IV penile squamous cell carcinoma treated with chemotherapy combined with Tislelizumab has a high objective response rate and controllable adverse reactions, A high proportion of patients with regional lymph node metastases had the opportunity to regain surgery or radiotherapy. It is expected to change the poor effect of chemotherapy alone for stage IV squamous cell carcinoma of penis. Clinical trial information: ChiCTR2000040095 .