Systemic Therapy for Non-Serous Ovarian Carcinoma

Yanin Chávarri-Guerra; Eduardo González-Ochoa; Héctor De-la-Mora-Molina; Enrique Soto-Perez-de-Celis


Chin Clin Oncol. 2020;9(4):52 

In This Article


CCC accounts for almost 10% of EOC.[44] There are differences in its prevalence by geographic area and/or ethnicity; for example, in East Asia the prevalence of ovarian CCC is higher[45] (23%) than in the United States (5%),[15] and this is also true when comparing Asian vs. Non-Hispanic White populations in the US (11.1% vs. 4.8%).[15] That being said, it is not clear whether this is due to genetic or environmental factors. CCC often presents at an early stage (stage I or II) compared to serous cancers[15,16] but both DFS and OS adjusted for stage is worse for patients with CCC,[15,46] which can be explained by the reduced sensitivity of CCC to platinum-based chemotherapy.[16,47]

The treatment strategy for CCC is very similar to that for other histologic types.[17,48] Despite the fact that these tumors may be more resistant to cytotoxic treatments, adjuvant chemotherapy should be strongly considered for all patients with early stage (I or II) CCC due to its poor prognosis, as clear-cell histology is considered to be a high-risk factor for recurrence.[16,47] Although there is limited evidence regarding the benefits of adjuvant chemotherapy in women with stage IA CCC, guidelines also recommend adjuvant treatment with a platinum-based doublet in these cases.[48–50] Other regimens, such as irinotecan plus cisplatin, have failed to demonstrate survival benefits.[51]

Advanced CCC should initially be treated with surgical cytoreduction (maximal debulking) followed by first-line chemotherapy.[17,48] While responses are much lower than for other subtypes, combination chemotherapy with paclitaxel plus platinum leads to improved survival in patients with advanced CCC, especially those with optimal cytoreduction.[18] Unfortunately, most women with advanced-stage CCC will relapse and require additional treatment. The prognosis of relapsing CCC is very poor when compared with serous carcinoma.[52] A retrospective Japanese study showed that, in both platinum-sensitive and platinum-resistant tumors, responses were observed in less than 10% of patients with CCC.[53] In general, no correlation between the efficacy of second line chemotherapy and histological subtypes has been shown due the small numbers of CCC included in trials of recurrent disease.[54,55]

The presence of specific molecular characteristics in CCC, such as the activation of the PI3K/AKT/mTOR, VEGF, IL-6/STAT3, MET, and HNF-1β pathways has been proposed as the reason for resistance to cytotoxic chemotherapy.[56] Therefore, pathway inhibitors are currently being evaluated as treatment strategies for CCC, either as single-agent therapies or in combination with cytotoxic agents. For example, the combination of temsirolimus with carboplatin/paclitaxel was investigated in patients with advanced CCC of the ovary. However, compared to conventional treatments, this regimen did not significantly increase PFS.[57]