Apatinib monotherapy for pretreated advanced squamous cell carcinoma of the penis: A phase II trial.

8 Background: Treatment options for patients with advanced penile squamous cell carcinoma who have disease progression on systemic chemotherapy are scarce. Antiangiogenic drugs have shown antitumor effects in case series. This phase 2 trial evaluated the activity and safety of apatinib (a VEGF receptor inhibitor) in such patients. Methods: This investigator-initiated, single-arm, phase 2 trial was performed at a tertiary cancer center in Shanghai, China. Eligible patients had histologically confirmed penile squamous cell carcinoma, were not candidates for surgery with curative intent, had measurable disease, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients were prescribed oral apatinib 500 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was the investigator-assessed overall response rate (ORR) assessed in all patients who received at least one dose of study drug. Results: Between 2016 and 2023, we enrolled 23 patients, all of whom received at least one dose of study treatment. Of the 23 patients, sixteen had an ECOG performance status of 2. Only six patients had human papillomavirous-positive tumors. Five patients had a partial response (ORR=22% (95%CI: 10%-42%). Median Progression-Free Survival was 3.8 months and median overall survival was 7.2 months. Treatment-related adverse events of grade 3 or worse occurred in 7 (30%) of 23 patients. The most common grade 3 or 4 treatment-related adverse events were hand–foot syndrome (13%), hypertension (9%), and increase in serum alanine aminotransferase (ALT:9%). No treatment-related deaths occurred. Conclusions: Apatinib in pretreated advanced penile cancer showed limited efficacy with a manageable safety profile. A prospective study with apatinib in combination with immune checkpoint therapy is ongoing. Clinical trial information: 000021849.