Abstract GS5-06: A U.S. food and drug administration pooled analysis of outcomes of older women with hormone-receptor positive metastatic breast cancer treated with a CDK4/6 inhibitor as initial endocrine based therapy

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

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Olaparib in hormone receptor-positive, HER2-negative metastatic breast cancer with a somatic BRCA2 mutation

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211006962 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110069

Author(s):

Lee S. Schwartzberg ◽

Lesli A. Kiedrowski

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Response ◽

Hormone Receptor ◽

Brca2 Mutation ◽

Locally Advanced ◽

Susceptibility Gene ◽

Metastatic Breast ◽

Breast Cancer Susceptibility Gene ◽

Hormone Receptor Positive

The oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib is approved for the treatment of patients with human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (mBC) and a germline breast cancer susceptibility gene (BRCA) mutation who have been treated with chemotherapy. This case report describes a 63-year-old postmenopausal woman with somatic BRCA2-mutated mBC who responded to olaparib treatment following multiple prior lines of therapy. The patient presented in January 2012 with locally advanced, hormone receptor-positive (HR+), HER2− BC which, despite initial response to neoadjuvant chemotherapy, recurred as bone disease in February 2014, and subsequently skin (June 2016) and liver (October 2016) metastases. A comprehensive 592-gene next-generation sequencing panel (Caris Life Sciences), performed on a skin biopsy, detected a pathogenic frameshift mutation in BRCA2 (H3154fs, c.9460delC), which was not identified in a 28-gene hereditary cancer germline analysis (Myriad Genetics, Inc.), and was therefore considered to be a somatic mutation. In January 2017, cell-free DNA (cfDNA) analysis (Guardant Health, Inc.) confirmed the BRCA2 H3154fs mutation in plasma. After several lines of chemotherapy and endocrine therapy, deriving clinical benefit from eribulin and capecitabine, the disease progressed by October 2017, and olaparib (300 mg orally twice daily) was initiated in January 2018. By April 2018, the liver lesions had shrunk by 80% and a >90% response in multiple skin lesions was noted. Clinical response was maintained for 8 months, followed by progression in the skin in September 2018. Biopsy of recurrent lesions revealed a novel BRCA2 mutation, E3152del (c.9455_9457delAGG), predicted to restore the open reading frame and presumably the mechanism of resistance to olaparib. Further likely resistance mutations were noted in subsequent cfDNA analyses. This case demonstrated a clinical response with olaparib as a later-line therapy for HR+, HER2− mBC with a somatic BRCA2 mutation.

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