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.

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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