Response of refractory metastatic cervical squamous cell carcinoma to sunitinib treatment

Background

In 2013 in Australia, the age-standardised incidence rate for cervical cancer was 6.8 cases per 100,000 females, and 813 people were newly diagnosed with cervical cancer.1 The rate and mortality of cervical cancer has halved since the National Cervical Screening Program was implemented in 1991.1 Although these improvements have been made, the prognosis of advanced or metastatic cervical cancer still remains poor.2

Treatment can be challenging for patients who present with advanced tumours as they face a complex interplay of physical, social, psychological and spiritual sequelae.3 For these patients, there may be few treatments proven to be effective,3 and patients with metastatic cancer may eventually exhaust treatment options.4 Molecular profiling provides a more personalised approach to cancer management in that it can be used to identify biomarkers in tumour samples. This information can then be used to guide treatment for patients with limited treatment options.5

Case Presentation

A 26-year-old woman was diagnosed in October 2011 with metastatic cervical cancer involving the posterior vaginal wall.

Investigations

Initial diagnosis was based on histopathological examination of a biopsy from the cervix, which confirmed a necrotic poorly differentiated squamous cell carcinoma. Subsequently, a computed tomography (CT) scan revealed pelvic side wall involvement, as well as metastases to the mediastinal-porta hepatis lymph node and possible early lung involvement.

After standard treatment options were exhausted, biopsy material was sent for tumour profiling analysis by Caris Molecular Intelligence. Tumour profiling revealed that the tumour had low thymidylate synthase (TS) expression and high topoisomerase 1 (TOPO1) expression, as well as overexpression of the HIF1A gene.

Treatment

In November 2011, after the initial diagnosis of metastatic cervical cancer involving the posterior vaginal wall, the patient was treated with two cycles of paclitaxel, ifosfamide and cisplatin.  However, progression was observed. The patient then received carboplatin with gemcitabine. No response was observed to this treatment. At this point, her pelvic disease was becoming more symptomatic. In February 2012, the patient received radiotherapy to the pelvis. This resulted in significant improvement in her pelvic symptoms and discharge.

Tumour profiling then revealed that the tumour had low TS expression and high TOPO1 expression. Given these findings, the patient began treatment with FOLFIRI. This treatment saw her quality of life improve, with a reduction in ECOG performance status from 2 to 1, a reduction in pain and a 2 kg weight increase. The treatment also led to 12 weeks of stable disease.

However, subsequently the disease progressed. The second treatment indicated by the tumour profiling results was sunitinib, based on overexpression of the HIF1A gene. The patient began treatment with sunitinib, and saw improvement in all clinical symptoms and complete response according to RECIST.

Figure 1. Whole body FDG-PET and PET scans taken before treatment with sunitinib and after 19 days of treatment. Scans show a complete response.

Figure 2.  Photographs before and after sunitinib treatment, revealing the complete resolution of palpable lymph nodes in the neck.

Outcome and Follow Up

Although treatment with sunitinib saw improvement in all clinical symptoms and complete response according to RECIST, the patient developed transection of the spinal cord from the complete disappearance of the disease from the vertebrae. At the time of her death from pneumonia 246 days later, she still remained in complete response. This case highlights the potential for improved quality of life and clinical response through treatment guided by tumour profiling.

 

Case Sources

  1. Dean A, Zeps N. Multi-targeted molecular profiling of advanced refractory solid tumour cancers: Influence on treatment choice and outcomes. Poster presented at MOGA Annual Scientific Meeting, Brisbane, 8-10 August 2011. [Full text]
  2. Dean A, Zeps N. Outcomes of molecular profiling-guided treatment in advanced refractory solid cancers: Follow-up and update on a single-centre experience. Poster presented at MOGA Annual Scientific Meeting, Melbourne, 1-2 August 2013. [Full text]

References

  1. Australian Institute of Health and Welfare. Cervical screening in Australia 2014-2015. 2017 (cited 26 June 2017). AIHW cat. no. CAN 104. Available from: [URL link]
  2. Cancer Research UK. Survival for cervical cancer. 2017 (cited 26 June 2017). Available from [URL link]
  3. Peppercorn JM, Smith TJ, Helft PR, et al. American Society of Clinical Oncology Statement: Toward individualized care for patients with advanced cancer. J Clin Onco 2011;29(6):755-60. [Full text]
  4. Von Hoff DD, Stephenson JJ, Rosen P, et al. Pilot study using molecular profiling of patients’ tumors to find potential target treatments for their refractory cancers. J Clin Oncol. 2010;28(33):4877-83. [Full text]
  5. Dean A, Byrne A, Marinova A, et al. Clinical outcomes of patients with rare and heavily pretreated solid tumors treated according to the results of tumor molecular profiling. Biomed Res Int. 2016;2016:4627214. [Full text]
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