Background.Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods. NALA was a randomized, activecontrolled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m 2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m 2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results. Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41-1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59-1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion. These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC. The Oncologist ;9999:• • Implications for Practice: In a subgroup of patients with central nervous system (CNS) metastases from HER2-positive breast cancer after two or more previous HER2-directed regimens, the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases,
IR occurred in 33% of the NAFLD patients, being more frequent among those with MC than among those with exposure to petrochemicals. The presence of IR in cases with advanced fibrosis suggests that it may influence the prognosis of NAFLD.
Background: The development of central nervous system (CNS) metastases presents a considerable challenge in metastatic breast cancer (MBC) due to the limited availability of evidence-based treatments. Up to 50% of patients with HER2-positive (HER2+) MBC develop CNS metastases during the course of their disease. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated activity against CNS metastases in HER2+ MBC in two phase 2 studies (NEfERT-T, TBCRC 022) and one phase 3 study (NALA); significant benefits for predefined CNS endpoints were reported in NEfERT-T and confirmed in NALA. Here we present an exploratory analysis of patients from NALA with CNS involvement at enrollment. Methods: NALA was an international, randomized, open-label, active-controlled, phase 3 study in patients with HER2+ MBC who had received ≥2 lines of HER2-directed therapy in the metastatic setting (ClinicalTrials.gov: NCT01808573). Patients with asymptomatic metastatic brain disease managed with stable doses of corticosteroids for ≥14 days prior to randomization were eligible, whereas patients with symptomatic or unstable brain metastases were excluded. Patients were randomized (1:1 ratio) to neratinib (N; 240 mg qd po) + capecitabine (C; 750 mg/m2 bid po) or lapatinib (L; 1250 mg qd po) + C (1000 mg/m2 bid po). Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Intervention for symptomatic metastatic CNS disease was a secondary endpoint. CNS disease at baseline was defined as patients with treated or untreated disease in the ‘brain’ assessed by investigator at enrollment. CNS imaging was not mandatory at screening. Results: Of the 621 patients enrolled in NALA, 101 (16%) had documented baseline CNS disease and 520 (74%) had no CNS disease at baseline. Patients with CNS disease had a lower performance status and were more likely to have hormone receptor-negative disease than those with no CNS disease; no major imbalances of baseline characteristics were noted between treatment arms. Overall, 78 (77%) patients had previously received CNS radiation [whole brain, n=59 (58%); stereotactic, n=17 (17%); unknown, n=2 (2%)], and 5 (5%) patients had undergone CNS surgery. Median treatment duration was 5.7 (IQR 2.8-8.5) months for N, and 3.5 (IQR 2.1-6.9) months for L. PFS, OS, and cumulative incidence of interventions for symptomatic CNS disease are summarized in the table. No new safety signals were detected. Conclusions: Regardless of the status of CNS metastases at baseline, patients appeared to have better outcomes in the N+C arm compared with the L+C arm. Table. Efficacy outcomes in patients with and without CNS disease at baselineIntention-to-treat (n=621)CNS metastases at baseline – Yes (n=101)CNS metastases at baseline – No (n=520)N+C (n=307)L+C (n=314)N+C (n=51)L+C (n=50)N+C (n=256)L+C (n=264)PFSaHazard ratio (95% CI)0.76 (0.63–0.93)0.66 (0.41–1.05)0.76 (0.62–0.94)P-value0.00590.07410.0099Restricted mean PFSb, months8.86.67.85.59.06.9Difference, months2.22.32.1OSHazard ratio (95% CI)0.88 (0.72–1.07)0.90 (0.59–1.38)0.85 (0.68–1.06)P-value0.20860.63520.1517Restricted mean OSb, months24.022.216.415.425.623.6Difference, months1.71.02.0Incidence of CNS interventionOverall cumulative incidencec, %22.7629.1940.1347.7919.1624.65P-value0.0430.4300.067aCentrally confirmed; bRestriction prespecified as 24 months for PFS, and 48 months for OS; c % requiring intervention for CNS disease (competing risk model) Citation Format: Cristina Saura, Larisa Ryvo, Sara Hurvitz, William Gradishar, Beverly Moy, Suzette Delaloge, Sung-Bae Kim, Mafalda Oliveira, Maureen Trudeau, Ming-Shen Dai, Barbara Haley, Ron Bose, Luciana Landeiro, Judith Bebchuk, Aimee Frazier, Kiana Keyvanjah, Richard Bryce, Adam Brufsky. Impact of neratinib on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-09.
PURPOSE An expert panel on breast cancer and COVID-19 disease was convened to address the impact of the COVID-19 pandemic for early breast cancer (eBC) management. METHODS To ensure that the most clinically relevant information was addressed, essential information was drawn from several of the latest national and international guidelines and another technical document. The expert panel met in five virtual closed sessions from November 2020 to May 2021 to consult on the relevant data from evidence-based results. The data gathered were discussed on an online platform. RESULTS This article reports the expert panel's highlights of these meetings' discussions. In addition, it provides practical recommendations covering topics regarding diagnosis, treatment, and management of patients with eBC in clinical settings routinely encountered by health care professionals amid the COVID-19 pandemic. CONCLUSION This article provided guidance on several topics regarding eBC management amid the COVID-19 pandemics to inform safer care practices.
122 Background: Paclitaxel is one of the most active drugs in BC and the weekly administration has been shown more effective and better. GEICAM9906 was a phase III trial that demonstrated the effectiveness and safety of a pragmatic dose-dense schedule of 100mg/m2 of paclitaxel given over 8 consecutive weeks (w), without G-CSF support. This schedule has been adopted at our institution in 2009 for HER2 negative disease and herein we present the first off-trial experience and also compare its safety profile with that of a historical cohort of pts treated with the conventional 80mg/m2 x12w schedule. Methods: The study consists of a retrospective review of medical files from pts with locally advanced BC treated with (neo)adjuvant paclitaxel-based therapy with one of two schedules: (1) 80 mg/m² x 12w or (2) 100 mg/m² x 8w. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE). Results: We reviewed files from 326 women with a median age of 52 (±10.9). Seventy and 256 pts received schedule (1) and (2), respectively. No significant difference was observed in the incidence of G3/4 toxicity: pneumonitis (2.8% vs 0.3% p=0.097), neuropathy (2.8% vs 0.7% p=0.303); hand-foot syndrome (1.4% vs 0.3% p=0.538); anaemia (0 vs 0.6% p=0.624); neutropenia (5.7% vs 6.2% p=0.408) with only one case of febrile neutropenia in schedule (2) arm; without cases of grade 3/4 thrombocytopenia, nausea, mucositis or anaphylaxis in both groups. Also, no significant difference was seen when comparing all grades toxicty. The dose intensity of paclitaxel was higher in schedule (2) with 97.72 mg/m² per week vs 77.07 mg/m² per week (p<0.0001). Conclusions: Weekly paclitaxel given according to GEICAM9906 is a pragmatic and well tolerated schedule when used in the Brazilian community setting, with a safety profile comparable to the conventional 80mg/m2 x12w schedule. In addition to being convenient to pts, it may also be cost-effective because of a lower number of clinic visits and infusions.
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