Dacomitinib induction therapy is active in human papillomavirus (HPV)-negative, locally advanced or metastatic penile squamous cell carcinoma (PSCC), according to findings from an open-label, single-arm, phase II study (abstract 399) presented at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held February 16–18 in Orlando, Florida.
“Dacomitinib is endowed with one of the highest single-agent objective response rates in PSCC,” said lead study author Andrea Necchi, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. “Overall survival rates were not influenced by post-dacomitinib chemotherapy.”
Long-term survival is rare for patients with PSCC involving the inguinal or pelvic lymph nodes. The standard treatment is surgery but it is “insufficient” as a stand-alone treatment, Necchi emphasized. “Multimodal approaches are warranted” but long-term chemotherapy outcomes are poor, he said. No effective treatments are available for patients with visceral metastases.
However, previous research suggests that anti-EGFR targeted therapy is active against PSCC in patients who have undergone chemotherapy.
Dacomitinib is an oral, irreversible pan-HER tyrosine kinase inhibitor that targets EGFR/HER1, HER2, and HER4. The study authors administered 45 mg/d to patients with PSCC who had not previously taken chemotherapy. CT and PET/CT scans were done every 8 weeks, and patients with responding locally advanced tumors were offered the choice of radical surgery. Objective response rates were evaluated using RECIST v1.1 criteria.
Between 2013 and 2016, 26 evaluable patients of an intent-to-treat sample of 28 patients, ages 18–75 years, participated in the study; 7 (26.9%) had visceral metastases. The objective response rate was 32.1% overall. Only 1 patient experienced a complete response; 8 patients (28.6%) experienced partial responses. Thirteen (46.4%) experienced stable disease, and 6 (21.4%) suffered disease progression. Necchi noted that 60.7%, or 17 patients, experienced a decrease in target lesions from baseline.
Overall progression-free survival (PFS) was 4.1 months, with a 6-month rate of 40.4%. Median PFS for patients with nodal involvement was 4.3 months, with a 6-month rate of 48.7%; and the median PFS for patients with visceral metastases was 3.2 months, with a 6-month rate of 16.7%.
Median overall survival was 13.7 months, with a 12-month rate of 54.9%. For patients with nodal involvement, the median was 20 months; and for those with visceral metastases, the median was 9.9 months.
PI3K/mTOR pathway genes, and TERT and IGF2R gene mutations were associated with better objective response. The mechanisms of response appeared to be EGFR mutation–independent, although downstream EGFR effectors such as PI3K/mTOR pathway genes require additional study. Angiogenesis gene mutations were associated with a larger proportion of non-responses. TP53/ATM mutations did not appear to affect response rates.
Treatment-related adverse events included grade 3 skin toxicity (3 patients (10.7%), as well as low-grade diarrhea, bleeding, and inguinal abscess.
Subsequent dacomitinib studies will need to evaluate longer treatment durations with or without chemotherapy or radiotherapy, concluded Necchi.