Platinum is recommended in combination with gemcitabine in the treatment of metastatic triple-negative breast cancer (mTNBC). We conduct a randomized phase 3, controlled, open-label trial to compare nab-paclitaxel/cisplatin (AP) with gemcitabine/cisplatin (GP) in mTNBC patients (ClinicalTrials.gov NCT02546934). 254 patients with untreated mTNBC randomly receive AP (nab-paclitaxel 125 mg/m² on day 1, 8 and cisplatin 75 mg/m² on day 1) or GP (gemcitabine 1250 mg/m² on day 1, 8 and cisplatin 75 mg/m² on day 1) intravenously every 3 weeks until progression disease, intolerable toxicity or withdrawal of consent. The primary endpoint is progression-free survival (PFS); secondary endpoints are objective response rate (ORR), safety and overall survival (OS). The trial has met pre-specified endpoints. The median PFS is 9.8 months with AP as compared to 7.4 months with GP (stratified HR, 0.67; 95% CI, 0.50–0.88; P = 0.004). AP significantly increases ORR (81.1% vs. 56.3%, P < 0.001) and prolongs OS (stratified HR, 0.62; 95% CI, 0.44–0.90; P = 0.010) to GP. Of grade 3 or 4 adverse events, a significantly higher incidence of neuropathy in AP and thrombocytopenia in GP is noted. These findings warrant further assessment of adding novel agents to the nab-paclitaxel/platinum backbone due to its high potency for patients with mTNBC.

A randomized phase II study of aromatase inhibitors plus metformin in pre-treated postmenopausal patients with hormone receptor positive metastatic breast cancer A randomized phase II study of aromatase inhibitors plus metformin in pre-treated postmenopausal patients with hormone receptor positive metastatic breast cancer

Purpose: We compared the clinical value of 16a-18F-fluoro-17b-estradiol (18F-FES) positron emission tomography (PET)/computed tomography (CT) and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT and investigated whether and how 18F-FES PET/CT affects the implemented management of newly diagnosed estrogen receptor positive breast cancer patients. Materials and Methods: We retrospectively analyzed 19 female patients newly diagnosed with immunohistochemistry-confirmed estrogen receptor (ER)-positive breast cancer who underwent 18F-FES and 18F-FDG PET/CT within 1 week in our center. The sensitivity of 18F-FES and 18F-FDG in diagnosed lesions were compared. To investigate the definite clinical impact of 18F-FES on managing patients with newly diagnosed ER positive breast cancer, we designed two kinds of questionnaires. Referring physicians completed the first questionnaire based on the 18F-FDG report to propose the treatment regime, and the second was completed immediately after reviewing the imaging report of 18F-FES to indicate intended management changes. Results: In total, 238 lesions were analyzed in 19 patients with newly diagnosed ER-positive breast cancer. Lesion detection was achieved in 216 sites with 18F-FES PET and in 197 sites with 18F-FDG PET/CT. These results corresponded to sensitivities of 90.8% for 18F-FES versus 82.8% for 18F-FDG PET/CT in diagnosed lesions. Thirty-five physicians were given the questionnaires referring to the treatment strategy, with 27 of them completing both questionnaires. The application of 18F-FES in addition to 18F-FDG PET/CT changed the management in 26.3% of the 19 patients with newly diagnosed ER-positive breast cancer. Conclusion: Performing 18F-FES PET/CT in newly diagnosed ER-positive breast cancer patients increases the value of diagnosis equivocal lesions and treatment management compared with 18F-FDG PET/CT. Implications for Practice: This study investigated whether 16a-18F-fluoro-17b-estradiol (18F-FES) positron emission tomography (PET)/computed tomography (CT) affects the clinical management of patients with newly diagnosed estrogen receptor (ER)-positive breast cancer. Physicians completing two questionnaires comparing the clinical impact of 18F-FES and 18F-FDG on individual management plans in patients with newly diagnosed ER-positive breast cancer confirmed that 18F-FES scans led to change in management in 26.3% of the 19 patients with newly diagnosed ER positive breast cancer. This retrospective study indicates the potential impact of 18F-FES PET/CT on intended management of patients with newly diagnosed estrogen receptor positive breast cancer in comparison to 18F-fluoro-2-deoxy-D-glucose PET/CT.

Endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) are standard treatment options for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) metastatic breast cancer (MBC). However, the efficacy of standard subsequent therapies after CDK4/6i-based treatment is unclear. This study aimed to examine physician practice patterns and treatment outcomes of subsequent therapies administered after progression on palbociclib therapy in clinical practice. The study included 200 patients with HR+/HER2– MBC who underwent subsequent treatments after progressing on palbociclib-based regimens in five Chinese institutions between August 2017 and April 2020. The treatment pattern, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were reported. A total of 200 patients were included, of whom 147 (73.5%) and 53 (26.5%) received subsequent chemotherapy and endocrine therapy, respectively. The frequently used monochemotherapy regimens were taxane (n = 29), capecitabine (n = 21), and vinorelbine (n = 17), while the endocrine therapy regimens were chidamide plus exemestane (n = 16) and everolimus plus exemestane (n = 9). The overall median PFS (mPFS) was 5.5 months, with no significant difference in mPFS between the chemotherapy and endocrine therapy groups (p = 0.669). However, among patients not sensitive to prior palbociclib treatment, those administered chemotherapy had significantly longer PFS than those administered endocrine therapy (p = 0.006). The mPFS with endocrine therapy after first-, second-, and subsequent-line palbociclib was 13.4, 3.1, and 4.1 months, respectively (p = 0.233); in contrast, the mPFS with chemotherapy was 7.2, 6.5, and 4.9 months after first-, second-, and subsequent-line palbociclib, respectively (p = 0.364). The median OS was not achieved. The ORR was 10.6% among the 198 patients included in the analysis. Physicians prefer chemotherapy over endocrine therapy for the treatment of patients with HR+/HER2– MBC who develop progression on palbociclib. Sensitivity to previous palbociclib treatment might be one of the indicators for predicting response to subsequent treatment. ClinicalTrials.gov identifier: NCT04517318

The present explorative study was initiated to evaluate the clinical value of ¹⁸F-FES PET/CT in monitoring the change of estrogen receptor (ER) expression and potential predictive value in metastatic breast cancer patients. Twenty-two pathology-confirmed breast cancer patients were prospectively enrolled and randomly divided into two groups (T: docetaxel, n = 14 and TF: docetaxel + fulvestrant, n = 8). The percentage of patients without disease progression after 12 months (PFS > 12 months) was 62.5% in group TF compared with 21.4% in group T (P = 0.08). According to ¹⁸F-FES PET/CT scans, the SUVmax (maximum standard uptake value) of all the metastatic lesions decreased in group TF after 2 cycles of treatment (6 weeks ± 3 days). However, 6 of 9 patients in group T had at least one lesion with higher post-treatment SUVmax. There was a significant difference in the reduction of ER expression between these two groups (P = 0.028). In group TF, the patients with PFS > 12 months had significantly greater SUVmax changes of ¹⁸F-FES than those with PFS < 12 months (PFS > 12 months: 91.0 ± 12.0% versus PFS < 12 months: 20.7 ± 16.2%; t = −4.64, P = 0.01). Our preliminary study showed that ¹⁸F-FES PET/CT, as a noninvasive method to monitor ER expression, could be utilized to predict prognosis based on changes in SUVmax.

Background: Predictive biomarkers are needed to identify oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer (MBC) patients who would likely benefit from cyclin-dependent kinase 4 and 6 inhibitors combined with endocrine therapy. Therefore, we performed an exploratory study to evaluate the tumour heterogeneity parameters based on 16α-¹⁸F-fluoro-17β-oestradiol (¹⁸F-FES)-PET imaging as a potential marker to predict progression-free survival (PFS) in MBC patients receiving palbociclib combined with endocrine therapy. Methods: Fifty-six ER + MBC patients underwent ¹⁸F-FES-PET/CT before the initiation of palbociclib. ¹⁸F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of ¹⁸F-FES-negative lesions. Intralesional heterogeneity was measured by the SUV-based heterogeneity index (HI = SUVmax/SUVmean). Association with survival was evaluated using the Cox proportional hazards model. Results: A total of 551 metastatic lesions were found in 56 patients: 507 lesions were identified as ¹⁸F-FES-positive, 38 lesions were distributed across 10 patients without ¹⁸F-FES uptake, and the remaining 6 were liver lesions. Forty-three patients obtained a clinical benefit, and 13 developed progressive disease (PD) within 24 weeks. Nine out of 10 patients with an ¹⁸F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only ¹⁸F-FES-positive lesions, only four patients had PD, and the median PFS was 23.6 months. There were statistically significant differences between the two groups (P < 0.001). For the subgroup of patients with only ¹⁸F-FES-positive lesions, low FES-HI patients experienced substantially longer PFS times than those with high FES-HI (26.5 months vs. 16.5 months, P = 0.004). Conclusions: ¹⁸F-FES-PET may provide a promising method for identifying and selecting candidate ER + /HER2- MBC patients who would most likely benefit from palbociclib combined with endocrine treatment and could serve as a predictive marker for treatment response. Trial registration NCT04992156, Date of registration: August 5, 2021 (retrospectively registered).