At the moment, there is no current agreed standard of care treatment for woman with ER-positive/HER2-negative metastatic breast cancer who progress on first-line treatment with CDK4/6 inhibitor plus aromatase inhibitor or selective oestrogen receptor degrader (SERD) [1-3]. CDK7 inhibition is a promising therapeutic strategy in cancer because it acts as a regulator of the cell cycle, transcription, and endocrine receptor signalling. Pre-clinical breast cancer models indicate the potential for synergy when the CDK7 inhibitor samuraciclib is combined with fulvestrant [4].
Prof. Charles Coombes (Imperial College London, UK) presented the results of a first-in-human, phase 2 trial with samuraciclib plus fulvestrant [5]. This single arm cohort assessed the tolerability and efficacy of samuraciclib in combination with standard dose fulvestrant in 31 patients with metastatic ER-positive/HER2-negative breast cancer who had previously received an aromatase inhibitor and a CDK4/6 inhibitor for advanced disease. The combination treatment was generally well tolerated, with adverse drug reactions of note being grade 1–2 nausea, vomiting, and diarrhoea. Most patients stayed on treatment until disease progression. No neutropenia was observed. Clinical benefit rate at 24 weeks was 36%. Clinical benefit rate in TP53 wildtype patients was 53%. Median progression-free survival for TP53 wildtype patients was 32 weeks versus 7.9 weeks for TP53 mutant patients. In addition, liver metastases were a negative predictive factor: median progression-free survival for patients without liver metastases was over 48 weeks versus 11.9 weeks for patients with liver metastases.
“These first results demonstrate that samuraciclib has an acceptable safety profile with evidence of anti-tumour activity in combination with fulvestrant for patients with metastatic ER-positive/HER2-negative breast cancer who have progressed on their prior CDK4/6 inhibitor,” concluded Prof. Coombes.
- Cook MM, et al. Oncologist 2021;26:101–106.
- Rugo HS, et al. Lancet Oncol 2021;22:489–498.
- Lindeman GJ, et al. J Clin Oncol 2021;39(Suppl):1004.
- Patel H, et al. Mol Cancer Therap 2018;17:1156–1166.
- Coombes C, et al. Study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in combination with fulvestrant in patients with advanced hormone receptor positive HER2 negative breast cancer (HR+BC). GS3-10, SABCS 2021 Virtual Meeting, 7–10 December.
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Table of Contents: SABCS 2021
Featured articles
Early-Stage Breast Cancer
Aromatase inhibitors outperform tamoxifen in premenopausal women
Concurrent taxane plus anthracycline most beneficial in reducing risk of breast cancer
Reduced risk of recurrence with ovarian suppression plus tamoxifen/exemestane
Metformin does not improve outcomes in patients with early-stage breast cancer
Omitting sentinel lymph node biopsy improves arm symptoms
HR-positive/HER2-negative Breast Cancer
Addition of palbociclib to standard endocrine therapy does not improve outcome in adjuvant treatment
The SERD elacestrant improves outcomes for patients unresponsive to endocrine therapy
Consistent overall survival benefit of ribociclib in advanced breast cancer
Premenopausal women benefit from adjuvant chemotherapy next to endocrine therapy
Promising anti-tumour activity of the CDK7-inhibitor samuraciclib plus fulvestrant
ctDNA is prognostic and predictive for response to ribociclib plus letrozole
Early switch to fulvestrant plus palbociclib beneficial for patients with ESR1 mutation
Triple-Negative Breast Cancer
Single-cell spatial analysis can predict response to neoadjuvant immunotherapy
Neoadjuvant pembrolizumab plus chemotherapy benefits event-free survival in TNBC
Early use of ctDNA testing can identify likelihood of relapse in TNBC
Pembrolizumab plus chemotherapy benefits patients with combined positive score ≥10
Neratinib plus trastuzumab plus fulvestrant shows encouraging clinical activity
Phase 1–3 Trials
Datopotamab deruxtecan shows promising anti-tumour activity
Trastuzumab deruxtecan outperforms trastuzumab emtansine
Nivolumab plus ipilimumab serve promising dual checkpoint inhibition
Entinostat plus exemestane improves progression-free survival in Chinese patients
Efficacy of pyrotinib plus capecitabine confirmed in previously treated patients
Basic and Translational Research
Using genomics to match treatments improves outcomes
Loss of ASXL1 tumour suppressor promotes resistance to CDK4/6 inhibitors
Inducers of ferroptosis are potential drugs to target p53-mutated TNBC cells
MAPK-pathway alterations are associated with resistance to anti-HER2 therapy
Genomic signatures of DCIS define biology and correlate with clinical outcomes
BRCA2 linked to inferior outcomes with CDK4/6 inhibitors plus endocrine therapy
Miscellaneous
Olaparib is well tolerated as an additional treatment
Race effects the likelihood to develop lymphoedema following breast cancer treatment
Sentinel lymph node staging is non-inferior to complete axillary lymph node dissection
One in 7 breast cancers detected during screening are overdiagnosed
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