Ovarian cancer is a type of cancer that begins in the ovaries.
It is the 7th most common cancer in women (excluding skin cancer) and the leading cause of death from gynecologic cancer in developed countries.
The 3 histologic types of ovarian cancer are epithelial (primarily seen in women >50 years of age), germ cell (most commonly seen in women <20 years of age) and sex cord stromal (rare and produces steroid hormones).
The median age at the time of diagnosis is 63 years old and >70% present with advanced disease.

    Sustained response with maintenance anti-VEGF therapy in a patient with clear cell ovarian cancer

    Dr Kitty Law
    Specialist in Clinical Oncology
    Hong Kong  

    Presentation and treatment
    This is the case of a 55-year-old lady who was first diagnosed with stage IIIB ovarian clear cell carcinoma (OCCC) and underwent radical surgery in March 2014. During the surgical procedure, some peritoneal deposits were found. Residual disease, however, was less than 1 cc in volume. Subsequently, the patient received adjuvant chemotherapy comprising eight cycles of Paclitaxel plus Carboplatin. PET-CT scan performed at the end of the treatment showed no definite disease.

    In May 2015, follow-up PET-CT scan showed ascites and peritoneal metastasis, as well as hypermetabolic uptake over the right external iliac lymph node. In June 2015, the patient was started on combination treatment with Gemcitabine, Carboplatin and Bevacizumab. She received six cycles of the combination therapy followed by maintenance therapy with Bevacizumab alone. PET-CT scan in December 2015 after initiation of the first cycle of maintenance therapy showed persistence of peritoneal metastasis.

    Figure 1.  PET-CT scan in December 2015 showing peritoneal deposits 

    DRC ovarian cancer case 7 fig 1

    Progress CT scan after cycle 6 showed shrinkage of the peritoneal metastasis. The peritoneal deposits remained static in size after the fifth cycle of maintenance therapy with Bevacizumab alone. Her ascites was reduced and the right external iliac lymph node showed stable disease. Interim PET-CT scan in May 2016 showed decrease in size of peritoneal deposits.

    Figure 2. PET-CT scan in May 2016 showing decrease in size of peritoneal deposits after 5 months of maintenance Bevacizumab monotherapy

    DRC ovarian cancer case 7 fig 2

    The patient has received 11 cycles of Bevacizumab as of early September 2016, and is scheduled for the next cycle in late September 2016. Maintenance Bevacizumab therapy will be given until disease progression.

    Treatment with chemotherapy/Bevacizumab was reasonably well tolerated. The patient experienced grade I and occasional grade II myelosuppression during treatment with chemotherapy plus Bevacizumab. However, she did not experience any significant toxicities during the Bevacizumab maintenance phase.

    OCCC is a distinct histopathologic subtype of epithelial ovarian cancer (EOC) and accounts for <5 percent of all ovarian malignancies. Clear cell carcinomas are considered high-grade tumours and the prognosis is generally poor. The current standard treatment for this type of tumour involves primary debulking surgery followed by taxane/platinum-based chemotherapy.1  

    Despite successful treatment with surgery and adjuvant chemotherapy, the majority of patients with OCCC will relapse, especially since most patients present with advanced disease, as in the case of our patient.2 Disease that relapses 6 months after completion of initial therapy is classified as platinum-sensitive, and re-treatment with platinum-based chemotherapy is an important part of management.3 Targeted therapy with Bevacizumab, an anti-VEGF agent, in combination with platinum-based chemotherapy has been shown to improve progression-free survival (PFS) in such patients. Our patient was thus treated based on such evidence. 

    The OCEANS trial (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-angiogenic Therapy in Platinum-sensitive Recurrent Disease), a randomized, phase III trial in 484 ovarian cancer patients with platinum-sensitive recurrence, demonstrated that those receiving 6-10 cycles of Carboplatin, Gemcitabine and Bevacizumab followed by maintenance Bevacizumab monotherapy until disease progression had improved median PFS compared with those receiving chemotherapy and placebo followed by placebo alone (12.4 vs 8.4 months; p<0.0001).4

    In addition, patients in the Bevacizumab arm had significantly improved objective response rate (78.5 vs 57.4 percent; p=0.0001) and duration of response (10.4 vs 7.4 months) vs those in the placebo arm. As for adverse events, Bevacizumab recipients more frequently experienced grade 3 or higher hypertension (17.4 vs 0.4 percent) and proteinuria (8.5 vs 0.9 percent). No new safety concerns arose in this study other than those previously reported with the use of Bevacizumab.

    However, the final overall survival (OS) analysis (median OS follow-up of 57.5 months) showed no significant difference in OS for patients treated with Bevacizumab vs placebo (33.6 vs 32.9 months; p=0.65).5  Nevertheless, as ovarian cancer becomes a chronic illness, treatments that prolong PFS, and therefore time without cytotoxic chemotherapy, become increasingly relevant. The latest Gynaecologic Cancer Intergroup consensus conference on ovarian cancer concluded that PFS is a valid endpoint for the assessment of treatment options for recurrent platinum-sensitive ovarian cancer.6 Our patient case is testimony to this recommendation as Bevacizumab-based therapy brought about disease control and was well tolerated.

    1. The Oncologist 2006;11:1089-1094.
    2. N Engl J Med 2004;351:2519-2529.
    3. J Clin Oncol 2006;24:4699-4707.
    4.  J Clin Oncol 2012;30:2039-2045.
    5. Gynecol Oncol 2015;139:10-16 .
    6. Int J Gynecol Cancer 2011;21:750-755.

    This special report is made possible through an unrestricted educational grant from the industry and first appeared in MIMS Oncology.
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