Atezolizumab does not improve survival in advanced penile cancer

The phase 2 PERICLES trial examining atezolizumab with or without radiotherapy in patients with advanced squamous cell carcinoma of the penis missed its primary endpoint of 1-year progression-free survival (PFS) ≥35%.

Patients with advanced squamous cell carcinoma of the penis have a poor prognosis and high morbidity, due to progressive locoregional disease [1]. Previous experimental studies in this setting did not prove to be successful [2,3]. Pre-clinical studies show high rates of infiltrating immune cells and high PD-L1 expression, suggesting that immunotherapy may be beneficial for these patients [4].

The single-centre, phase 2 PERICLES trial (NCT03686332) assessed the activity of atezolizumab with or without radiotherapy to control locoregional lymph node disease in patients with advanced squamous cell carcinoma of the penis. The study enrolled 32 patients with stage IV disease. Any previous treatment except for immunotherapy was allowed. All participants were treated with atezolizumab for a maximum of 1 year. Participants (n=20) expected to benefit from radiotherapy for locoregional disease control (cohort A) received additional radiotherapy. The primary endpoint was 1-year PFS for the full cohort. The primary objective target was 1-year PFS ≥35%. Dr Hielke-Martijn de Vries (Netherlands Cancer Institute, the Netherlands) presented the results [5].

The median PFS was 2.5 months and 1-year PFS was 12.5%, which did not meet the primary objective. Participants with PD-L1 positivity and those who were positive for human papillomavirus (HPV) showed slightly higher PFS (see Figure). The 2 patients who responded well to treatment were both PD-L1-positive and high-risk HPV-positive. The response rate was 33% (23% partial response and 10% complete response). Median overall survival was 11.5 months.

Figure: Progression-free and overall survival of patients, stratified by PD-L1 and HPV status [5]



In terms of toxicity, 20 patients (63%) across both arms experienced any grade of immunotherapy-related adverse events while 3 (9.4%) experienced grade 3 or 4 adverse events. In the radiotherapy arm, 18 patients (90%) experienced radiotherapy-related adverse events, with 13 (65%) being grade 3 or 4.

“Despite some evidence of anti-tumour activity from atezolizumab, the trial did not meet its endpoint,” concluded Dr de Vries. “The combination with radiotherapy did not improve outcomes of immunotherapy.”

1. Graafland NM, et al. Int J Cancer. 2011;128:426–432.
2. Djajadiningrat RS, et al. Clin Genitour Cancer. 2015;13:44–49.
3. Ottenhof S, et al. Eur Urol Suppl. 2019;18:e655.
4. de Vries H-M, et al. Eur Urol Focus. 2019;5:718–721.
5. de Vries H-M, et al. Clinical results of PERICLES: A phase II trial investigating atezolizumab +/- radiotherapy for advanced squamous cell carcinoma of the penis. Abstract 3, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202215 February 2024