Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Correlation of Preoperative Ki67 and Serum CA15.3 Levels with Outcome in Early Breast Cancers a Multi Institutional Study.

BACKGROUND: To investigate the association between preoperative pathological Ki67 labeling index and serum tumor marker cancer antigen 153 (CA 153) with clinicpathological parameters and treatment outcomes in early breast cancer. MATERIALS AND METHODS: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 68 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). RESULTS: A total of 280 pts was included. The median age was 49 years (3866 y) and median overall survival was 35 (2038) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. CONCLUSIONS: Preoperative Ki67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

Mammographic breast density: Predictive value for pathological response to neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: This study aims to evaluate the relation between mammographic breast density (BD) and pathological response to neoadjuvant chemotherapy. METHODS: In this retrospective study, 241 breast cancer patients who received neoadjuvant chemotherapy were included. BD was assessed in mammograms already performed at diagnosis. Pathological complete response (pCR) and pathological stage were correlated with BD, tumour phenotype and other clinico-pathological factors. RESULTS: Patients with low BD had better pCR compared to those with high density (30.5% vs 19.5% respectively, OR = 1.8, 95% CI = 0.98-3.3, p = 0.056) which was more pronounced after adjustment with body mass index (BMI) (OR = 2.4, 95% CI = 1.2-4.8, p = 0.011). HER2-positive disease (32.5% vs. 18.4%, OR = 2.2, 95% = 1.2-4.0, p = 0.01), lower BMI (OR = 1.1, 95% CI = 1.03-1.15, p = 0.004) and lower clinical stage (p = 0.002) were significant predictors of pCR in univariate analysis. In multivariate analysis, low BD (OR = 2.7, 95% CI = 1.3-5.5, p = 0.006) and lower BMI (OR = 1.1, 95% CI = 1.03-1.17, p = 0.003) were independent predictors of better pCR, while early clinical stage (I, II) was of borderline significance (OR = 2.6, 95% CI = 0.99-6.7, p = 0.052). High BD (OR = 1.8, 95% CI = 1.1-3.2, p = 0.03), advanced clinical stage (III) (OR = 1.5, 95% CI = 1.03-2.1, p = 0.03) and higher BMI (OR = 1.06, 95% CI = 1.02-1.11, p = 0.006) were significant predictors of advanced pathological stage. CONCLUSION: Low mammographic BD, low BMI and early clinical stage were associated with improved pCR rate and lower pathological stage after neoadjuvant chemotherapy. BD had more pronounced association with response to chemotherapy after adjustment with BMI.

Prophylaxis and treatment of venous thromboembolism in patients with cancer: the Saudi clinical practice guideline

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy. DESIGN AND SETTINGS: As a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer. METHODS: Six questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: Question 1. Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence).Question 2. Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence).Question 3. Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence).Question 4. Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence).Question 5. Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism? RECOMMENDATION: In patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence).Question 6. Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE? RECOMMENDATION: In patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).

Dabigatran, rivaroxaban and apixaban for extended venous thromboembolism treatment: network meta-analysis.

AIM: Many new oral anticoagulants (NOACs; dabigatran, rivaroxaban, and apixaban) are currently available to treat thromboembolic disease. There are no head-to-head trials comparing these agents. To assess the efficacy and safety of NOACs for prevention of recurrent venous thromboembolism (VTE), we performed a network meta-analysis. METHODS: Medline, Embase, and the Cochrane-controlled trial register were searched, without language restriction, to identify trials. Studies were evaluated according to a priori inclusion criteria and appraised using established internal validity criteria. Adjusted indirect comparisons between agents were performed using well-established methods. RESULTS: Three trials meeting inclusion criteria were identified. Direct comparison between apixaban 2.5 mg twice daily (BID) versus apixaban 5 mg BID showed no difference for any outcome. Clinically relevant non-major bleeding occurred less with both apixaban 2.5 mg BID (OR 0.23, 95% CI 0.08-0.62, P=0.004) and apixaban 5 mg BID [OR 0.31, 95% CI 0.11-0.82, P=0.019] compared to rivaroxaban 20 mg daily. Apixaban 2.5 mg BID showed less clinically relevant non-major bleeding than dabigatran 150 mg BID [OR 0.4, 95% CI 0.16-0.9, P=0.04], but not apixaban 5 mg BID. There were no differences between rivaroxaban 20 mg daily and dabigatran 150 mg BID. No differences in risk for recurrent VTE, major bleeding, or mortality were observed for any comparison between any pair of NOACs. CONCLUSION: There were no significant differences in risk for recurrent VTE, major bleeding, or all-cause mortality between the NOACs. However, apixaban 2.5 mg BID was associated with less clinically significant non-major bleeding than either rivaroxaban 20 mg daily or dabigatran 150 mg BID.