Gene signatures predict response to immunochemotherapy in triple negative breast cancers

December 2021 Cancer trials Nalinee Pathak

Triple negative breast cancers (TNBC) are considered to be the most aggressive subtypes of breast cancer. Due to the availability of only a few targeted medicines, the affected individuals have a poorer prognosis than other types of breast cancer.

Recent clinical trials with immune checkpoint inhibitor (ICI) treatment have significantly improved clinical outcomes in TNBC patients. However, there remains a lack of precise biomarkers to predict response to neoadjuvant immunochemotherapy (durvalumab; PD-L1 blocker). Recently, Toshiaki et al. have developed a 27-gene immune-oncology (IO) signature and evaluated the accuracy of these gene signatures in predicting pathological complete response (pCR) of TNBC to neoadjuvant immunochemotherapy.

Study design

Between 18 December 2015 and 21 November 2018, 59 patients were enrolled in the study, with seven patients included during phase I and the remaining 52 during phase II. Patients in phase I received durvalumab either 3 mg/kg every 2 weeks (n=4) or 10 mg/kg every 2 weeks (n=3), whereas 10mg/kg every 2 weeks was assessed for efficacy in phase II (n=52). The primary efficacy endpoint of the study was pCR, defined as the absence of residual invasive tumour on hematoxylin and eosin evaluation of the breast surgical specimen and all resected regional lymph nodes following completion of neoadjuvant immunochemotherapy. The odds of achieving primary efficacy endpoint (pCR) were compared by three biomarkers: 27-gene signature obtained by core-needle biopsy, 101-gene signature from which the 27-gene signature was derived, and positive PD-L1 expression by immunohistochemistry (IHC).

Results

The pCR rate amongst 55 patients was 45 % (25/55). The odds of achieving pCR was highest with 27-gene signature (odds ratio [OR]: 4.13; P=0.012) followed by 101-gene signature (OR: 3.14; P=0.054), and finally PD-L1 positivity by IHC (OR: 2.63; P=0.106). Importantly, odds of achieving pCR were significantly increased with the combination of the 27-gene signature plus PD-L1 expression by IHC (OR: 6.53; P=0.003).

Conclusion

The 27-gene IO signatures can successfully predict the pCR of TNBC patients to neoadjuvant immunochemotherapy. Further evaluation of these gene markers is needed in a larger cohort.

Reference

Iwase T, Blenman KRM, Li X, et al. A Novel Immunomodulatory 27-Gene Signature to Predict Response to Neoadjuvant Immunochemotherapy for Primary Triple-Negative Breast Cancer. Cancers (Basel). 2021 Sep 28;13:4839.

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