An individual patient data meta-analysis failed to demonstrate that receipt of adjuvant therapy provided a clear benefit for women with POLE-mutated endometrial cancer, according to the results of a study published in Cancer. The study researchers reported that endometrial cancers with these somatic mutations have unfavorable pathologic features, but women with POLE-mutated endometrial cancer seem to have good survival outcomes.
In this study, researchers conducted an individual patient data meta-analysis using data from 359 women with POLE-mutated endometrial cancer from studies that took place in March 2012 to March 2018. The majority (82%) had pathogenic mutations. The most common pathogenic mutations were P286R (51%) and V411 (31%). Sixty-five (18%) of the patients had nonpathogenic POLE mutations and experienced worse outcomes (hazard ratio [HR]=3.42; 95% CI, 1.47-7.58; P <.01).
Among women with pathogenic POLE mutations, traditional prognosticators were not associated with progression, recurrence, or death from disease, with the exception of stage (P <.01). Adverse events were rare among this group as well. There were 11 progressions or recurrences and 3 disease-specific deaths. Even among patients with recurrence, salvage rates were high and sustained, with 8 of these patients alive without evidence of disease.
The researchers noted that the reasons for giving or not giving adjuvant therapy could not be ascertained from the studies. However, it appeared that younger age was associated with a higher likelihood of receiving adjuvant therapy (P <.001). Treatment also was associated with unfavorable histopathologic features.
Adjuvant treatment was not associated with outcome. Although almost 10% of the patients with POLE mutations were at stage III or IV, only 3 adverse events occurred in those with advanced-stage disease.
“While we await maturation of prospective clinical trials assessing the safety of withholding treatment from women with early-stage [POLE-mutated endometrial cancers], the data presented herein support a move to implementation of molecular classification for all women with [endometrial cancers],” the researchers concluded.
Disclosures: Several of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ affiliations.
McAlpine JN, Chiu DS, Nout RA, et al. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: an individual patient data meta-analysis. Cancer. Published online April 1, 2021. doi:10.1002/cancr.33516