SG study underpins novel Tx strategies for OCCC

A study from Singapore shows that targeted therapies such as bevacizumab, immune checkpoint inhibitors (ICIs), and secondary cytoreductive surgery (SCS) hold promise for the treatment of ovarian clear cell carcinoma (OCCC).

“OCCC is relatively chemoresistant, with poorer stage-adjusted outcomes … Our study provides real-world evidence of encouraging responses to antiangiogenic therapy and ICI in a multiethnic Asian cohort with OCCC,” said the researchers. “Our findings also demonstrate excellent survival outcomes with SCS, supporting its consideration in carefully selected patients with relapsed OCCC.”

The team retrospectively evaluated data from 172 OCCC patients (median age at diagnosis 53 years) treated at their institution from January 2000 to May 2022. About 71 percent of participants were Chinese, while the rest were either Malay (11.6 percent), Indian (7.6 percent), or of other descent (9.9 percent). [J Gynecol Oncol 2024;35:e69]

Early-stage OCCC

A total of 110 patients had early-stage (stage I/II) OCCC. After primary debulking surgery, 105 had no residual disease at the time of surgical closure. Eighty-nine received adjuvant chemotherapy. At follow-up, two-thirds (n=73) were in remission, while the rest (n=37) relapsed.

Those who received adjuvant chemo had numerically better relapse-free survival than those who did not (median 162.9 vs 109.2 months; hazard ratio [HR], 0.57; log-rank p=0.19); relapse was similar between groups (odds ratio [OR], 1.02).

Relapsed disease

Of the 37 who relapsed, 34 underwent systemic therapy and received platinum-based chemo as first-line (1L) treatment in the relapsed setting. Four patients also received bevacizumab concurrently and as maintenance treatment. Twenty-nine patients received prior adjuvant chemo postop.

About three-quarters (75.9 percent) had a platinum-free interval (PFI) of ≥6 months, while the rest had a PFI of <6 months. Compared with the latter group, the former had better 1L overall response rate (ORR; 70 percent vs 42.9 percent; OR, 3.1) and median progression-free survival (PFS; 16 vs 7.9 months; HR, 0.13; p=0.002).

Advanced disease

Sixty-two patients had de novo advanced disease (stage III/IV). Of these, 53 underwent systemic treatment and received platinum-based chemo as 1L therapy, while nine received bevacizumab concurrent with chemo and as maintenance treatment. 1L ORR was 56.9 percent, median PFS was 8.2 months, and median overall survival (OS) was 26.5 months.

Bevacizumab, PD(L)1 ICI for relapsed/advanced OCCC

Thirteen patients with relapsed/advanced disease received platinum-based chemo + bevacizumab followed by maintenance bevacizumab as 1L treatment; 72 received platinum-based chemo only. Add-on bevacizumab was tied to a numerically longer 1L PFS vs chemo only (median 12.2 vs 9.3 months; HR, 0.69; p=0.33).

Among 27 patients who received second- or later-line PD(L)1 ICI, median PFS was 2.9 months, ORR was 18.5 percent, and median duration of response was 7.4 months.

SCS for selected relapsed OCCC patients

Of those who relapsed after primary surgery, 17 underwent SCS. The median relapse-free interval from primary surgery was 32.8 months. Post-SCS, 13 received further adjuvant chemo with platinum-based doublets and liposomal doxorubicin. Median PFS and OS were 35 months and 96.8 months, respectively.

Of note, most of these patients had early-stage disease, complete debulking with no residual disease at surgery, and <3 disease sites at relapse.

According to the researchers, the excellent survival outcomes in this subset of well-selected patients suggest that SCS should be explored in selected relapsed OCCC patients.

More trials warranted

OCCC is a rare histological subtype of epithelial ovarian cancer (EOC) with a distinct epidemiology and molecular profile. Albeit rare, up to 25 percent of diagnosed EOCs in Singapore, Japan, and South Korea are OCCCs. [J Obstet Gynaecol Res 2017;43:1667-1677; J Gynecol Oncol 2016;27:e5]

The researchers underlined the need for collaborative trials based on the disease’s clinical and distinct molecular characteristics to develop individualized treatment approaches and improve clinical outcomes.