Background: In the Phase III MONALEESA (ML) trials, ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + endocrine therapy (ET) significantly improved progression-free survival (PFS) vs placebo (PBO) + ET in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Here we report key patient-reported outcomes (PROs) for pts treated with RIB-based regimens of interest (i.e. with a non-steroidal aromatase inhibitor [NSAI] or fulvestrant [FUL]) in the ML-2, -3, and -7 trials. Methods: Postmenopausal pts with HR+, HER2– ABC and no prior ET for advanced disease received RIB (600 mg/day; 3-weeks-on/1-week-off) + letrozole (2.5 mg/day; ML-2 [NCT01958021]), or FUL (500 mg every 28 days, with an additional dose on Day 15 of Cycle [C] 1; ML-3 [no prior ET for ABC subgroup only; NCT02422615]). Premenopausal pts with no prior ET and ≤1 line of chemotherapy for advanced disease received RIB + NSAI (anastrozole [1 mg/day]/letrozole [2.5 mg/day]) + goserelin (3.6 mg every 28 days; ML-7 [NCT02278120]). The primary endpoint for all trials was PFS. PROs were a secondary endpoint of all trials and were evaluated using EORTC QLQ-C30, QLQ-BR23 (ML-2 and ML-7), EQ-5D-5L, WPAI-GH (ML-7 only), and BPI-SF (ML-3 only) questionnaires. Changes from baseline and time to 10% deterioration (TTD) in health-related quality of life (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression models, respectively. Results: A total of 1530 pts were included in this analysis. Questionnaire compliance was high across trials (ML-2/ML-3: >90%; ML-7: >80%). On-treatment HRQoL (EORTC QLQ-C30 global health status/quality of life [QoL] score) was maintained from baseline up to C34, C28, and C17 in both treatment arms for ML-2, ML-3, and ML-7, respectively. In ML-7, mean overall HRQoL scores continued to improve in the RIB arm from C18 to C28, but scores decreased in the PBO arm. At end of treatment, mean overall HRQoL scores decreased in both arms across trials. Median TTD (RIB vs PBO) was similar between arms, favoring the RIB arms (ML-2: 27.7 vs 27.6 months; hazard ratio 0.944; 95% confidence interval [CI] 0.720–1.237; ML-3: not reached [NR] vs 22.4 months; hazard ratio 0.721; 95% CI 0.484–1.074; ML-7: 24.0 vs 19.4 months; hazard ratio 0.759; 95% CI 0.561–1.028). Clinically meaningful reductions in EORTC QLQ-C30 pain score (>5 points from baseline) were observed in the RIB arm of ML-2 from as early as C3 and were sustained vs only at C7 and C13 in the PBO arm. Clinically meaningful reductions in pain were observed from C22 to C28 in the RIB arm of ML-7 vs only at C28 in the PBO arm. In ML-3, clinically meaningful reductions in pain were observed from C3 to C5, C11–17, and at C22 and C28 in the RIB arm vs C17–C25 in the PBO arm. Furthermore, median TTD of the BPI-SF pain severity index score was NR in either arm of ML-3 (hazard ratio 0.858; 95% CI 0.554–1.330). Conclusions: In addition to significantly prolonging PFS, RIB consistently maintains QoL regardless of ET combination partner. RIB + ET is also associated with clinically meaningful reductions in pain vs PBO + ET across a broad population of pts with HR+, HER2– ABC. Citation Format: Beck JT, Neven P, Esteva FJ, Bardia A, Harbeck N, Hurvitz S, O'Shaughnessy J, Verma S, Lanoue B, Alam J, Kong O, Chandiwana D, Chia S. Patient-reported outcomes with ribociclib-based therapy in hormone receptor-positive, HER2-negative advanced breast cancer: results from the phase III MONALEESA-2, -3, and -7 trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-14.
Introduction: In the setting of pre-operative neoadjuvant chemotherapy (NAC) for the treatment of breast cancer, it is important to ensure coordination between medical and surgical oncology. A study by Sanford et al. show that patients receiving surgery >8 weeks after NAC have worse overall survival. As NAC continues to expand its role in breast cancer treatment, a closer look at the maximal acceptable time between NAC and surgery becomes more important. We wished to assess the impact of time between last dose of chemotherapy and surgery on pathological complete response (pCR), disease free survival (DFS), overall survival (OS), and surgical complications. Methods: A cohort study was conducted utilizing the BC Cancer Agency's prospective neoadjuvant database, located in Vancouver, BC. Patients were selected if they had undergone NAC with curative intent for treatment of breast cancer, followed by surgical resection. Patients who received neoadjuvant radiation and/or hormone therapy were excluded. Patients were divided into three groups: those who had surgery <4 weeks from last dose of chemo, 4-8 weeks from last dose, and >8 weeks from last dose. Charts were audited for demographic data, tumour characteristics, and complications from surgery. Data was analyzed using a Chi Squared test to determine any differences in pCR, OS, DFS, and surgical complications, between the three different time intervals. Results: 347 patients were identified and included in this study. The median time to surgery after last dose of chemotherapy was 4.86 weeks (range 0.86-22.86 weeks). The percentage of patients that achieved pCR was 31.3%, 30.5%, and 28.6% in the <4 weeks, 4-8 weeks, and >8 weeks groups respectively (p= NS for all comparisons). There was no difference in pCR observed between the three groups based on receptor status. At the median follow up of 3 years, DFS was 85%, 85.8%, and 85.7% in all three groups. Likewise OS was 95%, 90%, and 89% respectively. The rate of surgical complications are 16%, 23.4%, and 21.4% for the three groups respectively (p=NS). Conclusions: This study demonstrated no difference between receiving surgery <4 weeks, 4-8 weeks, or >8 weeks after last dose of NAC on pCR, survival, or surgical complications. This finding was preserved in all receptor subtypes. This has important implications for resource allocation. This data may also help in counselling and easing patient anxiety in terms of the urgency (or lack thereof) and wait times for surgery. Subsequent studies with larger sample sizes will help to ensure that clinical differences in outcomes are not affected by wait times. Comparison of outcome measures based on needle to knife time < 4 weeks (n=80)4-8 weeks (n=239)>8weeks (n=28)p (<4 weeks vs. < 8 weeks)pCR31.3% (25)30.5% (73)28.6% (8)0.791HR+Her2-4.5% (1/22)6.5% (6/92)0% (0/5)--TNBC31.5% (6/19)42.1% (24/57)0% (0/6)--Her2+46.1% (18/39)48.8% (44/90)47.1% (8/17)--3 year DFS85%85.5%85.7%0.9273 year OS95%90%89%0.290Surgical Complication16.3%23.4%21.4%0.536 Citation Format: Lai V, Hajjaj O, Chia S, Simmons C. Needle-to-knife wait time and impact on pCR in patients undergoing neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-04.
Background: The international, randomized, placebo-controlled phase III ExteNET trial showed that 1 year (yr) of neratinib 240 mg/day after trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (iDFS) in 2840 patients with early-stage HER2+ breast cancer at 2 yr (hazard ratio 0.67; 95% CI 0.50–0.91; p=0.009) [Chan 2016] and 5 yr (hazard ratio 0.73; 95% CI 0.57-0.92; p=0.008) [Martin 2017]. A prespecified subgroup analysis by hormone receptor (HR) status suggested enhanced efficacy with neratinib in patients with HR+ (2-yr hazard ratio 0.51; 95% CI 0.33–0.77) vs. HR– tumors (2-yr hazard ratio 0.93; 95% CI 0.60–1.43). The efficacy of neratinib was also greater in patients who initiated treatment within 1 yr of prior trastuzumab compared with those who started neratinib later. The European Medicines Agency's Committee for Medicinal Products for Human Use recently recommended neratinib for use in patients with HR+ tumors who initiate treatment within 1 yr of completing trastuzumab-based adjuvant therapy. Subgroup analyses from ExteNET examining iDFS benefits in this patient population are presented here. Methods: Patients with early-stage HER2+ breast cancer who completed trastuzumab-based (neo)adjuvant therapy were assigned to oral neratinib 240 mg/day or placebo for 1 yr. Randomization was stratified by HR status (determined locally before trial entry), nodal status, and trastuzumab regimen. Endocrine therapy was allowed in patients with HR+ disease. The primary endpoint, iDFS, was tested by 2-sided log-rank test and hazard ratios (95% CI) were estimated using Cox proportional hazards models. Kaplan-Meier methods were used to estimate iDFS rates. Secondary endpoints were DFS-DCIS, time to distant recurrence, distant DFS, and CNS recurrences. The primary analysis was conducted at 2 yr, and a sensitivity analysis conducted at 5 yr. Clinicaltrials.gov:NCT00878709. Results: Of the 2840 patients (neratinib, n=1420; placebo, n=1420), 1631 (57%) had HR+ disease (neratinib, n=816; placebo, n=815). Most (93%) HR+ patients were receiving endocrine therapy at baseline. 1334 of 1631 (82%) patients with HR+ tumors were randomized to start neratinib within 1 yr of last trastuzumab dose (neratinib, n=670; placebo, n=664). iDFS benefits from neratinib in this population are shown in the table. Secondary endpoints were also improved with neratinib vs. placebo in this population. Safety data in this subset will be presented at the meeting. Table. iDFS in patients with an interval between last trastuzumab dose and randomization of ≤1 yr HR+ population (N=1334)ITT population (N=2297) Hazard ratiob Hazard ratiob Δ, %a(95% CI)P-valueΔ, %a(95% CI)P-value2-yr analysisc+4.50.490.002+2.90.630.006 (0.30–0.78) (0.45–0.88) 5-yr analysisd+5.10.580.002+3.20.700.006 (0.41–0.82) (0.54–0.90) aDifference in iDFS rates between neratinib vs. placebo; bNeratinib vs. placebo; cData cut-off: July 2014; dData cut-off: March 2017 Conclusions: Neratinib may have enhanced and sustained efficacy in patients with HR+ disease who initiate treatment within 1 yr of trastuzumab-based adjuvant therapy. Citation Format: Gnant M, Martin M, Holmes F-A, Jackisch C, Chia SK, Iwata H, Moy B, Martinez N, Mansi J, Morales S, Ruiz-Borrego M, von Minckwitz G, Buyse M, Delaloge S, Bhandari M, Murias Rosales A, Galeano T, Fujita T, Luczak A, Barrios CH, Saura C, Rugo HS, Chien J, Johnston SR, Spencer M, Xu F, Barnett B, Chan A, Ejlertsen B. Efficacy of neratinib in hormone receptor-positive patients who initiated treatment within 1 year of completing trastuzumab-based adjuvant therapy in HER2+ early-stage breast cancer: Subgroup analyses from the phase III ExteNET trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-13-01.
Background: The rapidly evolving landscape of systemic treatment for metastatic breast cancer (MBC) during the 1990s led to meaningful improvements in the overall survival (OS) of MBC patients[1]. Despite ongoing and expanded access to new treatments, it remains unclear if this has translated into further advances in survival. Moreover, the prognosis of MBC patients based on subtype, over time, are also important to differentiate. Methods: The BC Cancer Breast Cancer Outcomes Unit (BCOU) database was utilized to identify patients referred to BC Cancer who were diagnosed with MBC during 3 time cohorts (cohort 1:2003-2005; cohort 2:2007-2009; cohort 3:2011-2013), to reflect changes in MBC treatment over these separate time periods. Baseline clinical and pathological criteria were compiled, in addition to adjuvant treatments received, as well as number of lines of treatment in the metastatic setting. OS was compared across time cohorts for all patients and then between subtypes using Kaplan-Meier survival curves. Results: A total of 3,953 patients met the inclusion criteria, consisting of 2,440 (61.7%) estrogen-receptor positive (ER+), 778 (19.7%) HER2 positive and 542 (13.7%) triple-negative breast cancer (TNBC) patients. One hundred and ninety-three patients (4.9%) were unable to be subtyped and were therefore excluded from the analysis . A total of 2,205 (90.4%) ER+ patients received at least 1 line of systemic therapy, with 80.0% receiving at least 1 line of hormonal therapy. The median time on hormonal treatment was 8.9 months (range 0.03 - 156.7) for first-line and 6.1 months (range 0.1 – 173.3) for second-line. In the HER2+ group, 665 (85.5%) patients received at least 1 line of treatment, with a median of 2 lines of treatment (range 1-16). Median duration of anti-HER2 treatment was 6.7 months (range 0.03 - 163.8) with a median of 1 line of anti-HER2 directed treatment (range 1-5). For TNBC patients, 357 (65.9%) received at least 1 line of treatment, with a median of 2 (range 1-10). No significant differences in OS were observed between the 3 time cohorts, with a median overall survival (mOS) of 1.63 years, 1.37 years and 1.57 years in cohorts 1-3, respectively (p=0.12).When comparing across subtypes, the ER+ group faired best with a mOS of 1.96 years (95% CI 1.8-2.1), consistent across time cohorts (p=0.72). This was followed by the HER2+ group with a mOS of 1.53 years (95% CI 1.3-1.7), also consistent across time cohorts (p=0.31). The TNBC group faired worst, with a mOS of 0.67 years (95% CI 0.6-0.8) over time (p=0.87). Conclusions: Despite advances in systemic therapy since the early 2000s, no meaningful improvements in overall survival were observed over time, regardless of subtype. It remains to be seen if developments since 2013 will lead to gains in overall survival for MBC patients, at a real life, population-based level. [1]Chia SK, Speers CH, D'yachkova Y, et al. Cancer 2007;110:973-979. Citation Format: LeVasseur N, Fiorino L, Speers CH, Aparicio M, Lohrisch C, Chia SK. Prognosis and survival in metastatic breast cancer – Ten years in review, a population-based analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-16-05.
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