Dr. Vineet Talwar discusses a patient case of penile cancer in which he highlights how Cetuximab can be an effective second- and third-line treatment option for patients progressing on standard chemotherapy.

Localised penile cancers are treated surgically while metastatic penile cancer is treated with standard chemotherapy. There have been very few case reports on targeted therapy with Cetuximab in treatment of recurrent and metastatic penile cancers that have failed standard chemotherapy.

Here, we report a case series of a patient who improved on Cetuximab after progressing with standard chemotherapy regimens. There were no available clinical trials for penile cancer patients who progressed beyond the standard surgical therapy and chemotherapy. So, this report may support the use of targeted therapy in such patients.

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The treatment and prognosis of penile cancer depends on the stage of the disease along with the presence and extent of lymph node involvement. Surgical resection is the primary treatment for early-stage penile squamous cell carcinoma, which is the most common histologic type of cancer. [1] However, disease recurrence develops frequently after surgery. For locally advanced or metastatic penile cancers, a multidisciplinary approach involving surgery, radiotherapy, and systemic chemotherapy is required. [2,3] The most commonly used chemotherapy agents are Cisplatin, Fuorouracil, Ifosfamide, and Paclitaxel. But these drugs have very short-term responses. [4,5] Recently, targeted therapy with epidermal growth factor receptor (EGFR) antibodies, have been found to be efficacious in the treatment of advanced penile cancers. [6-7]

In this case series, the patient had ultimately progressed on chemotherapy, and they received anti-EGFR antibody with an oral chemotherapy (cetuximab and capecitabine).

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Case report

A 60-year-old hypertensive, non-diabetic, who had myocardial infarction 20 years ago was diagnosed to have well differentiated squamous cell carcinoma of penis and underwent partial penectomy in May 2017. He had isolated inguinal lymph node recurrence in September 2018. The patient was not willing for further surgery and hence concurrent CT (Paclitaxel and Carboplatin) with local RT was given. In view of progressive disease on re-evaluation with CT abdomen and pelvis, palliative right inguinal lymph node dissection with hemi-scrotectomy, DIEP flap and STSG graft reconstruction was done in March 2019. HPE was suggestive of poorly differentiated squamous cell carcinoma with infiltration of skin, dermis, and subcutis. He was started on Cetuximab and Capecitabine based chemotherapy from May 2019.

After 3 cycles of therapy the patient had partial response to therapy. After 6 cycles of therapy, CT chest and abdomen revealed progressive mediastinal, pelvic, and mediastinal lymphadenopathy. In view of weakness of left hand and left foot with paraesthesias, MRI brain was done, which showed supra and infratentorial brain metastases. Palliative EBRT to brain was given. Despite being MMR proficient, Pembrolizumab was started from November 2019 as the PD-L1 TPS was 20% and multiple lines of treatment were given already. Patient was lost to follow up after 2 cycles of immunotherapy.

After receiving two cycles of Paclitaxel and Carboplatin based palliative chemotherapy, he had progressive inguinal lymphadenopathy. Hence, the patient was started on Cetuximab and Capecitabine from August 2019. After 3 months patient had stable disease. He underwent WLE of fungating mass in right inguinal region + bilateral ILND + right pelvic lymph node dissection + ALT island FLAP reconstruction. He received adjuvant RT to local site. He is on follow up.

Discussion

The EGFR-RAS-RAF signaling pathway plays an important role in the regulation of tumor cell proliferation, survival, angiogenesis, invasion, and metastasis. Gou et al, [8] investigated 4 essential molecules in the EGFR-RAS-RAF signaling pathway in a large series of patients with penile squamous cell cancers (pSCC). The results showed EGFR overexpression rate of 92%. Few pSCC cases successfully treated with anti-EGFR mAbs have also been reported. A study with 28 patients receiving anti-EGFR drugs such as Cetuximab, Panitumumab, and Nimotuzumab had 50% of patients showing a response to treatment. 15 of 28 patients were receiving anti-EGFR therapy as second-line therapy. Overall, 50% of the patients showed response to treatment with median PFS of 3 months.

Rescigno et al. reported a partial response in an elderly man with pSCC using Docetaxel plus Cetuximab after failure of the Cisplatin regimen. There has also been a case report of locally advanced pSCC that was successfully resected after using Cetuximab with chemotherapy as neoadjuvant treatment.

In a case series by Gavin Hui et al., [9] two patients with metastatic pSCC were treated with EGFR antibody and anti-PD-L1 antibody. Our patient progressed on Cetuximab and was still able to receive next line treatment (immunotherapy). One patient in the above study [9] had additional 12 months survival after starting anti -EGFR therapy which is like our case. Similar Some of the patients may require multi-modal therapy with Cetuximab, Capecitabine, surgical resection and radiation therapy.

Cetuximab may play a role in controlling the recurrent carcinoma penis along with chemotherapy. Cetuximab is an effective second- and third-line treatment option for patients progressing on standard chemotherapy.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Vineet Talwar is the Director, Department of Medical Oncology at Rajiv Gandhi Cancer Institute, Delhi.