First‐line programmed death receptor‐1 (PD‐1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum‐based chemotherapy, for stage IV penile cancer

Abstract

Objectives To evaluate the anti‐tumour activity and safety of anti‐programmed death receptor‐1 (PD‐1) antibody plus epidermal growth factor receptor blockade combined with platinum‐based chemotherapy (PEP) as first‐line therapy for stage IV penile squamous cell carcinoma (PSCC). Patients and Methods We conducted a retrospective review of 17 patients with stage IV PSCC undergoing first‐line PEP at Sun Yat‐sen University Cancer Center between January 2018 and September 2021. Clinical responses were assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events version 5.0. Results Of 17 patients who received first‐line PEP, 13 were observed to have partial responses. Twelve patients subsequently received consolidated surgery. Nine of these achieved pN0 status, of whom six with locally advanced PSCC achieved pathological complete response. The median (range) follow‐up time was 24.87 (3.63–29.40) months. Median PFS and median OS were not reached, with 2‐year PFS and OS rates being 68.4% (95% confidence interval [CI] 48.7–96.1) and 62.9% (95% CI 41.6–95), respectively. Eight patients experienced Grade 3 or 4 treatment‐related AEs. No Grade 5 AEs or death associated with treatment was observed. Conclusions Anti‐PD‐1 antibody plus epidermal growth factor receptor blockade and platinum‐based chemotherapy showed promising anti‐tumour activity, acceptable toxicity, and satisfying long‐term survival for stage IV PSCC. Larger clinical trials are needed to validate our findings.

Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor–based combination therapy

“…Our previous work using combined therapy including ICI showed satisfactory ORR (76.5%), whereas a numerical but not statistical difference in ORR was found between the HPVþ and HPV-groups (100% vs. 66.7%), mainly due to the limited number of patients. 5 Therefore, we included more patients in this study and conducted the largest study to date that specifically analyzed the correlation between HPV status, treatment efficiency, and prognosis in advanced PSCC treated with PCT.…”

“…Patients receiving first-line PCT had not received any systemic treatment previously and had proper indications for PCT due to high-risk features signifying inferior response and poor prognosis after traditional regimens, as described in our previous study. 5 Patients with multi-line PCT (eight in the second-line setting and three in the third-line setting) had disease progression after previous systemic regimens or relapsed less than 6 months after the final neoadjuvant or adjuvant systematic therapy. Patients were informed of the possible benefits and risks before PCT, and all patients provided signed informed consent.…”

“…Several studies on immune checkpoint inhibitor (ICI) monotherapy or combination treatment against progressive PSCC reported an objective response rate (ORR) of 13.0%–16.7% and median overall survival (OS) of 9.8–11.3 months 3,4 . Moreover, we previously reported a better ORR (76.5%) and 2‐year OS rate (62.9%) among 17 advanced‐stage IV PSCCs treated with ICI plus chemotherapy and targeted therapy 5 . These studies indicate the potential of immunotherapy; however, it is imperative to select a subset of patients suitable for ICI monotherapy and ICI‐based combination treatment.…”

“…3,4 Moreover, we previously reported a better ORR (76.5%) and 2-year OS rate (62.9%) among 17 advanced-stage IV PSCCs treated with ICI plus chemotherapy and targeted therapy. 5 These studies indicate the potential of immunotherapy; however, it is imperative to select a subset of patients suitable for ICI monotherapy and ICI-based combination treatment.…”

An Analysis of Nectin-4 (PVRL4) in Penile Squamous Cell Carcinoma

“…Targeted monoclonal antibody–based therapies (eg, cetuximab and panitumumab) and various immune checkpoint inhibitors are being assessed either alone or in combination with other agents, although mostly in the setting of grouped histology basket trials [2] , [3] . Recently, promising tumor control was described in 17 patients with stage IV PSCC treated with combined platinum-based chemotherapy, epidermal growth factor receptor blockade, and anti–programmed death receptor-1 (anti–PD-1) antibody [4] . Despite these efforts, there remains a great need to identify novel therapeutic targets in this patient population.…”