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We quantify the commute time savings associated with work from home, drawing on data for 27 countries. The average daily time savings when working from home are 72 minutes in our sample. We estimate that work from home saved about two hours per week per worker in 2021 and 2022, and that it will save about one hour per week per worker after the pandemic ends. Workers allocate 40 percent of their time savings to their jobs and about 11 percent to caregiving activities. People living with children allocate more of their time savings to caregiving.

Background The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−), PIK3CA‐mutated advanced breast cancer (ABC), after cyclin‐dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real‐world setting. Materials and Methods Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real‐world patient cohort who received standard‐of‐care from a deidentified clinico‐genomics database (CGDB). Primary and secondary endpoints were to compare progression‐free survival (PFS), estimated by the Kaplan‐Meier method, and the proportion of patients remaining progression‐free at 6 months, respectively, between the two cohorts. Results A total of 855 patients with PIK3CA‐mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2‐targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real‐world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real‐world cohort, and 6‐month PFS was 54.6% versus 40.1%, respectively. Conclusion Matched/weighted analysis comparing BYLieve with the real‐world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2−, PIK3CA‐mutant ABC after CDK4/6i treatment. Implications for Practice Approximately 40% of patients with hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−) advanced breast cancer (ABC) have PIK3CA‐mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α‐selective phosphatidylinositol‐3‐kinase inhibitor, demonstrated significantly improved progression‐free survival in SOLAR‐1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real‐world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2−, PIK3CA‐mutant ABC in the post‐CDK4/6i setting., This article reports the efficacy of treatment with alpelisib combined with fulvestrant in a cohort of patients with PIK3CA‐mutated breast cancer compared with the effectiveness of real‐world standard treatments in the post‐CDK4/6i setting using data from a deidentified clinico‐genomics database (CGDB).

Summary Background Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. Methods This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov , NCT03056755 . Findings Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5–15·9). 61 (50·4%; 95% CI 41·2–59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. Interpretation BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. Funding Novartis Pharmaceuticals.

Background: The MONALEESA (ML) studies showed significant PFS & OS benefits for 1L ribociclib (RIB) + endocrine therapy (ET) in patients (pts) with pre/peri & postmenopausal advanced breast cancer. The benefit of RIB beyond study treatment (tx) was also observed, with improvements in PFS2 & delays in time to 1st subsequent chemotherapy (CT). While there is currently no preferred tx for the next line post-progression on a CDK4/6 inhibitor (CDK4/6i), except alpelisib in pts with a PIK3CA mutation, guidelines encourage multiple lines of ET or ET-based therapies before switching to CT (except for visceral crisis). This pooled exploratory analysis of the ML studies examined outcomes of various tx strategies post progression on RIB + ET. Methods: Data from pts receiving 1L therapy in ML-2, -3, & -7 (NSAI cohort only & excluding pts with early relapse [≤ 12 mo after end of (neo)adjuvant ET] whose prognosis is closer to that of 2L pts) were pooled & pts receiving 1st subsequent therapies after progression were analyzed. Three groups of subsequent therapies were assessed: ET only, CT, & targeted therapy. Subsequent CT comprises CT +/- any other therapy; targeted therapy includes CDK4/6i, mTORi, PI3Ki, AKTi, etc, +/- ET. Subsequent CT & targeted therapy groups are mutually exclusive. Median duration of study tx, 1st subsequent therapy, & OS (from randomization to death) were analyzed by KM methods. Weighted Cox regressions were performed using inversed propensity scoring matching method (inverse probability tx weighting [IPTW]) to ensure compatible pt characteristics between tx arms. These are not randomized comparisons; only baseline characteristics were used for the estimation of propensity scores in the IPTW, imbalance of prognostic factors at progression may exist. Results: Median follow-up time was 74 mo. 461 pts treated with RIB (81%) & 440 (86%) with PBO discontinued study tx & received a subsequent therapy. In the RIB arms, the most common 1st subsequent therapies were ET only (40%), CT (29%), combination with targeted therapy (28%), & other (4%); for the PBO arms, 34% received CT as a 1st subsequent therapy & 31% each received ET only or combination with targeted therapy (5% received other). In 14% & 20% of pts in the RIB & PBO arms, the 1st subsequent therapy was a CDK4/6i, of these 31% & 12% were RIB. In general, regardless of type of 1st subsequent therapy, the duration of both the study tx & the 1st subsequent therapy was longer for pts treated with RIB vs PBO (Table). In both RIB & PBO arms, pts who received subsequent CT had the shortest duration on study tx, whereas those who received subsequent targeted therapy combination had the longest. Among pts on 1L RIB + ET, after matching pre-randomization baseline characteristics, subsequent CDK4/6i use was associated with the longest mOS (84 [84-NE] mo), followed by ET only (60 [51-68] mo), then a non-CDK4/6i targeted therapy (52 [43-72] mo); post-progression CT was associated with the shortest mOS (37 [32-48] mo). Conclusions: This large, pooled analysis of the ML studies shows that, in general, duration of any subsequent therapy was numerically longer post-1L RIB + ET vs PBO + ET, & subsequent CT was used less frequently for pts on RIB vs PBO. Both findings confirm that upfront tx with RIB does not worsen pt outcomes. This trend in enhancement of outcomes of subsequent therapies seen with 1L RIB suggests a post-tx effect that merits further exploration. Citation Format: Erika Hamilton, Laura M. Spring, Peter A. Fasching, Sandra Franco, Richard H DeBoer, Javier Cortés, Kevin Kalinsky, Dejan Juric, Aditya Bardia, Sina Haftchenary, Agnes Lteif, Juan Pablo Zarate, Liyi Cen, Patrick Neven. Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer in the MONALEESA-2, -3, and -7 studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-42.

To evaluate the effect of lapatinib on the QTc interval and ECG parameters in patients with advanced solid tumors. This was a multicenter, placebo-controlled study in subjects with advanced solid tumors. Subjects were administered two doses of matching placebo on day 1, 12 h apart and one dose in the morning on day 2. Two doses of lapatinib 2000 mg were administered orally on day 3, 12 h apart and one dose in the morning on day 4. Twelve-lead digital ECGs were extracted from continuous Holter recordings at pre-specified time points over the 24-h period on days 2 and 4. Venous blood samples for lapatinib concentrations were obtained immediately following the ECGs. A maximum mean baseline-adjusted, placebo time-matched increase in QTcF, (ddQTcF) in the evaluable, (EV) population (n = 37) of 8.8 ms (90% CI 4.1, 13.4) occurred approximately 10 h after the third lapatinib dose. These results were consistent with those in the pharmacodynamic, PD population, (n = 52) (ddQTcF = 7.9 ms; 90% CI 4.1, 11.7). No subject experienced QTcF increases from baseline of > 60 ms on lapatinib or placebo. The geometric mean lapatinib Cmax of 3902 ng/mL was observed at 3.6 h post-dose. These data show a relevant, treatment-related increase in QTcF after treatment with three doses of lapatinib 2000 mg. This study confirms the need for caution in patients with solid tumors treated with lapatinib, and who are concomitantly receiving drugs that are strong CYP3A inhibitors and/or prolong the QTc.

BACKGROUND: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months). PATIENTS AND METHODS: This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2- ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). RESULTS: Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug-drug interaction between ribociclib and fulvestrant or new safety signals were observed. CONCLUSIONS: This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy. ispartof: ANNALS OF ONCOLOGY vol:32 issue:8 pages:1015-1024 ispartof: location:England status: published

Objectives: A multicenter, noninterventional, observational study was conducted in the Latin American countries including Argentina, Brazil, Colombia, Mexico, and Venezuela to assess the prevalence of liver and cardiac iron overload using magnetic resonance imaging (MRI) in patients with chronic anemias except thalassemia. Methods: Patients aged >10 years with transfusion-dependent anemias, except thalassemia, either with 2000 ng/mL or with ≥20 units of RBC transfusions regardless of SF level in their lifetime, were enrolled. Iron overload was assessed using MRI. Results: Among 175 patients included, the majority had sickle cell disease (SCD; 52%), followed by aplastic anemia (AA; 17.7%), myelodysplastic syndrome (MDS; 8.6%), Diamond-Blackfan anemia (DBA; 4%), pure red cell aplasia (1.1%), and others (16.6%). Liver iron overload was observed in 76.4% of patients, while cardiac iron overload was seen in 19.2% when assessed by MRI. The prevalence of iron overload was 80.2% in patients with SCD, 73.3% in MDS, 77.4% in AA, 100% in pure red cell aplasia, 71.4% in DBA, and 68.9% in other transfusion-related disorders. A moderate correlation between liver iron concentration (LIC) and SF was observed in patients with SCD and MDS (r = 0.47 and r = 0.61, respectively). All adverse events reported were consistent with the published data for deferasirox or underlying disease. Conclusion: A high prevalence of iron overload in this patient population in Latin American countries indicates that a better diagnosis and management of iron overload is required in these countries.

Background This pooled analysis of MONALEESA trials evaluated the safety of ribociclib plus endocrine therapy (RIB + ET) with a focus on dose reductions in first-line patients. Methods In the dose reduction analysis, data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET) and MONALEESA-7 (patients receiving combination therapy with an NSAI as initial ET). Efficacy was analysed by ribociclib relative dose intensity (DI). Safety was analysed in all patients in the trials (except those receiving tamoxifen in MONALEESA-7) and those with/without ≥1 ribociclib dose reduction. Results Of 818 women who received first-line RIB + ET, 41.8% required ≥1 dose reduction due to AEs (most commonly, neutropenia). Median RIB relative DI in patients without and with dose reductions was 99.3% and 65.6% in MONALEESA-2, 98.4% and 67.8% in MONALEESA-3 and 98·0% and 66·3% in MONALEESA-7. Median PFS was 24.8, 24.9 and 29.6 months for patients who received ≤71% (30th percentile), 72-96% (60th percentile) and 97-100% (90th percentile) RIB relative DI, respectively. No new safety signals emerged in the pooled safety analysis. Conclusions This analysis provides reassuring data showing that the clinical benefit of RIB is preserved when dose modifications are undertaken to manage AEs. Trial registration MONALEESA-2 (NCT01958021) first posted October 8, 2013; MONALEESA-3 (NCT02422615) first posted April 21, 2015; MONALEESA-7 (NCT02278120) first posted October 29, 2014.

Background: The MONALEESA (ML)-2, -3, and -7 trials have shown a significant benefit in overall survival (OS) with ribociclib (RIB) + endocrine therapy (ET) over placebo (PBO) + ET in HR+/HER2− advanced breast cancer. HR+ breast cancer is a clinically and biologically heterogeneous disease, with identified intrinsic subtypes that vary in incidence, survival rate, and response to treatment. In a pooled analysis of the ML studies, patients with both luminal and HER2-enriched (HER2E) subtypes exhibited a consistent progression-free survival benefit with RIB + ET. The HER2E subtype (RIB, 14%; PBO, 11%), which is associated with ET resistance and poor outcomes, exhibited the greatest relative reduction in risk of progression or death (61%) with RIB + ET. Here, we report a pooled analysis of the ML-2, -3, and -7 trials, presenting OS by intrinsic subtype.. Methods: Tumor samples from patients enrolled in the ML-2, -3, and -7 trials underwent PAM50-based subtyping (blinded from clinical data), and the correlation between intrinsic subtype and OS was analyzed. Gene expression profiling of formalin-fixed, paraffin-embedded tumor samples was performed using a customized NanoString nCounter GX 800-gene panel. The prognostic and/or predictive relationship between PAM50-based subtypes and OS was evaluated using univariable and multivariable Cox proportional hazards models. Multivariable models were adjusted for known clinical prognostic factors, including age, prior chemotherapy, prior ET, ECOG performance status, visceral disease (presence of liver/lung metastases), bone-only metastases, histological grade, number of metastatic sites, tumor type, and de novo metastatic disease.. Results: From the pooled patient population (N = 2066), 997 tumor (71% primary) samples from the RIB (n = 585) and PBO (n = 412) arms of the ML trials (ML-2, n = 318; ML-3, n = 414; ML-7, n = 265) were profiled. Subtype distribution was consistent across treatment arms (Table). A similar benefit with RIB vs PBO was observed in the ITT (hazard ratio [HR], 0.76; 95% CI, 0.67-0.86) and biomarker (HR, 0.75; 95% CI, 0.63-0.89) populations. In both univariable and multivariable analyses, intrinsic subtype was prognostic for OS in both the RIB and PBO arms (P < .0001 for both arms); patients with luminal A subtype had the best OS outcomes in both arms, whereas patients with basal-like subtype had the worst OS outcomes. Intrinsic subtype was also predictive of OS (subtype-treatment interaction: P = .016 [univariable], P = .007 [multivariable]) with a consistent OS benefit with RIB treatment in all subtypes except for basal-like (Table). Patients with HER2E (HR, 0.60; P = .018), luminal B (HR, 0.69; P = .023), and luminal A (HR, 0.75; P = .021) subtypes all derived benefit from RIB. In patients with the basal-like subtype (n = 30), the HR was 1.89 (P = .148); these results should be interpreted with caution due to the small sample size (3% in each arm) and exploratory nature of this analysis.Conclusions: This pooled analysis of the ML trials confirmed the prognostic and predictive value of intrinsic subtype (PAM50 based) for OS. The addition of RIB to ET resulted in consistent OS benefit across all subtypes except for basal-like. The. consistent survival benefit in the HER2E subtype, which is associated with endocrine resistance and a very poor prognosis compared with luminal disease, warrants further investigation. SubtypeTreatment ArmDistribution, n (%)OS, median (95% CI), monthsHR (95% CI)P ValueaLuminal ARIB320 (55)68.0 (61.5-NR)0.75 (0.58-0.96).021PBO222 (54)54.6 (48.3-66.2)Luminal BRIB154 (26)58.8 (48.3-79.2)0.69 (0.50-0.95).023PBO124 (30)44.9 (35.5-52.6)HER2-enrichedRIB95 (16)40.3 (33.4-49.0)0.60 (0.40-0.92).018PBO52 (13)29.4 (23.9-42.0)Basal-likeRIB16 (3)19.4 (10.7-33.2)1.89 (0.80-4.47).148PBO14 (3)21.2 (12.8-NR)aP values are all two-sided. NR, not reached. Citation Format: Lisa Carey, Nadia Solovieff, Fabrice André, Joyce O'Shaughnessy, David A Cameron, Wolfgang Janni, Gabe S Sonke, Yoon-Sim Yap, Denise A Yardley, Juan Pablo Zarate, Tetiana Taran, Faye Su, Agnes Lteif, Aleix Prat. Correlative analysis of overall survival by intrinsic subtype across the MONALEESA-2, -3, and -7 studies of ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS2-00.

Background: MONALEESA-2 (ML-2) recently reported a statistically significant overall survival (OS) benefit with first-line ribociclib (RIB) + letrozole (LET) over placebo (PBO) + LET in postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) (median, 63.9 vs 51.4 months; hazard ratio, 0.76; 95% CI, 0.63-0.93; P = .004). Understanding OS outcomes in clinically relevant subgroups of patients is important for improving personalized care and prognosis. Here, we report the results of a prespecified exploratory OS analysis in select patient subgroups by baseline location and number of metastatic sites.. Methods: Postmenopausal patients with HR+/HER2− ABC were randomized 1:1 to receive first-line RIB or PBO with LET. Prespecified exploratory OS analyses were performed for subgroups of special interest by baseline location (bone only [yes or no], liver involvement [yes or no], liver or lung involvement [yes or no]) and number of metastatic sites (< 3 or ≥ 3). The data are hypothesis generating since this analysis was exploratory and not powered for statistical significance.. Results: A total of 668 patients were included in the analysis. A consistent improvement in OS was observed with RIB + LET vs PBO + LET in all subgroups regardless of baseline metastatic site (Table). RIB + LET demonstrated an OS benefit over PBO + LET in clinically relevant subgroups by baseline location and number of metastatic sites, including subgroups of patients with liver metastases, liver or lung metastases, and ≥ 3 metastatic sites, who generally have a worse prognosis.. Conclusion: Consistent with the intent-to-treat population of ML-2, the results of this prespecified exploratory analysis demonstrated an OS benefit with RIB + LET independent of the site and number of metastatic lesions. TableTreatment Arm (n)HR (95% CI)Bone-only metastasisYesRIB + LET (69)0.78 (0.50-1.21)PBO + LET (79)NoRIB + LET (265)0.77(0.61-0.96)PBO + LET (255)Liver involvementYesRIB + LET (59)0.81 (0.54-1.24)PBO + LET (72)NoRIB + LET (275)0.77 (0.62-0.97)PBO + LET (262)Liver or lung involvementYesRIB + LET (182)0.81(0.62-1.05)PBO + LET (190)NoRIB + LET (152)0.71 (0.53-0.96)PBO + LET (144)No. of metastatic sites< 3RIB + LET (220)0.78(0.61-1.00)PBO + LET (222)≥ 3RIB + LET (114)0.71(0.51-0.98)PBO + LET (112) Citation Format: Joyce O'Shaughnessy, Salomon M Stemmer, Howard A Burris, Yoon-Sim Yap, Gabe Sonke, Lowell Hart, Mario Campone, Katarina Petrakova, Eric P Winer, Wolfgang Janni, Pierfranco Conte, David A Cameron, Fabrice André, Carlos Arteaga, Juan Pablo Zarate, Arunava Chakravartty, Tetiana Taran, Fabienne Le Gac, Paolo Serra, Gabriel N Hortobagyi. Overall survival subgroup analysis by metastatic site from the phase 3 MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with advanced HR+/HER2− breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS2-01.

Background: In MONALEESA-2, -3, and -7, ribociclib plus endocrine therapy (ET) prolonged progression-free survival (PFS) versus placebo plus ET in women with hormone receptor-positive, HER2– advanced breast cancer (ABC). This pooled analysis of the MONALEESA studies further evaluated the safety of ribociclib plus ET and provides insight into the efficacy of ribociclib based on dose intensity (DI). Methods: Data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET), and MONALEESA-7 (patients receiving combination therapy with an NSAI as initial ET). Efficacy (PFS, overall response rate [ORR], and clinical benefit rate [CBR]) was analyzed according to ribociclib relative dose intensity. Safety was analyzed in all patients and those with and without ≥1 ribociclib dose reduction. Findings: The adverse event (AE) profile in the 1066 and 823 women in this analysis who received ribociclib plus ET and placebo plus ET, respectively, was consistent with previous reports. All-grade neutropenia (74% vs 5%) and nausea (45% vs 27%) were the most common AEs with ribociclib vs placebo, and neutropenia was the most frequent grade 3/4 AE (60% vs 2%). Across MONALEESA-2, -3 and -7, 41.8% of patients (range, 32.8% to 54.5%) required ≥1 dose reduction due to AEs (most commonly, neutropenia). Median ribociclib relative DI in patients without and with dose reductions was 99.3% and 65.6% in MONALEESA-2, 98.4% and 67.8% in MONALEESA-3, and 98.0% and 66.3% in MONALEESA-7. Median PFS was 24.8, 24.9, and 29.6 months for patients who received 30th, 60th, and 90th percentile ribociclib relative DI, respectively, with a numerically higher ORR observed in the lowest relative DI group. Interpretation: This analysis confirms the safety profile of ribociclib plus ET in women with HR+/HER2– advanced breast cancer and demonstrates that the clinical benefit of ribociclib is preserved when dose modifications are undertaken to manage AEs. Trial Registration: MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), MONALEESA-7 (NCT02278120) Funding Statement: MONALEESA-2, -3, and -7 were supported by Novartis Pharmaceuticals Corporation. Declaration of Interests: Dr. Burris reports consulting or advisory for AstraZeneca, Bristol-Myers Squibb, FORMA Therapeutics, Janssen, MedImmune, Mersana, Novartis, Roche/Genentech, TG Therapeutics; grants from AbbVie, Agios, AstraZeneva, Bayer, BioMed Valley Discoveries, Boehringer Ingleheim, Bristol-Myers Squibb, Celgene, Celdex, CytomX Therapeutics, eFFECTOR Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Incyte, Janssen, Jounce Therapeutics, Lilly, Loxo, Macrogenics, MedImmune, Merck, Mersana, Milennium, Moderna Therapeutics, Novartis, Pfizer, PTC Therapeutics, Roche/Genentech, Seattle Genetics, Takeda, Tarveda Therapeutics, Tesaro, TG Therapeutics, Valent Technologies, Vasastern, Vertex; Dr. Chan has nothing to disclose; Dr. Bardia reports consulting or advisory for Immunomedics, Pfizer, Novartis, Genentech/Roche, Merck, Radius Health, Spectrum Pharma, Taiho Pharma, Biothernostics Inc., Sanofi, Daichi Pharma, Puma; personal fees from Biothernostics Inc., Pfizer, Novartis, Genentech/Roche, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho Pharma, Sanofi, Daiichi Pharma, Puma; grants from Genentech/Roche, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Mersana, Innocrin, Biothernostics Inc.; Dr. Beck has nothing to disclose; Dr. Sohn has nothing to disclose; Dr. Neven has nothing to disclose; Dr. Tripathy reports consulting or advisory for Novartis, Pfizer, Genomic Health, GlaxoSmithKline; personal fees from Novartis, Pfizer, Genomic Health, GlaxoSmithKline; research grant from Novartis; Dr. Im reports consulting or advisory for AstraZeneca, Novartis, Hanmi, Pfizer, Eisai, Amgen, MediPacto, Genentech/Roche, Lilly; personal fees from AstraZeneca, Novartis, Hanmi, Pfizer, Eisai, Amgen; MediPacto, Genentech/Roche, Lilly; grants from AstraZeneca, Pfizer, Genentech/Roche; Dr. Chia reports consulting or advisory for Novartis, Pfizer, Hoffman LaRoche, Eli Lilly; personal fees from Novartis, Pfizer, Hoffman LaRoche, Eli Lilly; Dr. Esteva reports consulting or advisory for Novartis, Pfizer, Genentech/Roche, Celltrion Healthcare, Seattle Genetics; personal fees from Novartis, Pfizer, Genentech/Roche, Celltrion Healthcare, Seattle Genetics; grants from Novartis, Pfizer, GlaxoSmithKline, Genentech/Roche; Dr. Hart reports consulting or advisory for Novartis; personal fees from Novartis; grants from Novartis; Dr. Zarate reports employment and stock ownership from Novartis; Dr. Antonia Ridolfi reports employment and stock ownership from Novartis; Dr. Rodriguez-Lorenc reports employment and stock ownership from Novartis; Dr. Yardley reports consulting or advisory for Biothernostics Inc., Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, NanoString Technologies, Novartis; personal fees from Biothernostics Inc., Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, NanoString Technologies, Novartis; grants from Daiichi Sankyo, Lilly, Eisai, Novartis, Abbvie, AstraZeneca, Clovis Oncology, Immunomedics, InventisBio, Lilly, MedImmune, Medivation, Merck, Oncothyreon, Pfizer, Syndax, Tesaro. Ethics Approval Statement: All studies were conducted in accordance with Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki. The institutional review board at each participating center reviewed the protocol and any amendments, and all patients provided written informed consent.

1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB. Methods: Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized. Results: At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB + FUL continued to demonstrate an OS benefit vs PBO + FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO + FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB + FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed. Conclusions: The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO. Clinical trial information: NCT02422615 .[Table: see text]

1006 Background: PIK3CA mutations (mut) occur in ~40% of pts with HR+, HER2– ABC and are associated with poor prognosis and resistance to treatment (tx). ALP, a PI3Kα inhibitor, plus FUL demonstrated efficacy in the phase 3 SOLAR-1 trial of HR+, HER2– PIK3CA-mut ABC. Little clinical data and few prospective studies are available to inform tx decisions for pts with HR+, HER2– PIK3CA-mut ABC in the post-CDKi setting. BYLieve is the first trial evaluating ALP + endocrine therapy (ET; FUL or letrozole) in pts with HR+, HER2– PIK3CA-mut ABC who progressed on/after prior therapy, including CDKi. In this ongoing phase 2, open-label, noncomparative study, 112 pts with centrally confirmed PIK3CA mut in tumor tissue are enrolled in each cohort per immediate prior tx of CDKi + AI, CDKi + FUL, or systemic chemo or ET. Enrollment is complete in prior CDKi + AI and CDKi + FUL cohorts and ongoing in prior systemic chemo or ET cohort. We report on the cohort of pts with CDKi + AI as immediate prior tx. Methods: Pts received ALP 300 mg/day + FUL 500 mg Q28D + C1D15. Primary endpoint was proportion of pts alive without disease progression at 6 mo per local assessment; 2-sided 95% confidence intervals (CI) were calculated using Clopper and Pearson (1934) exact method. Evidence of clinically meaningful tx effect was defined as the lower bound of the 95% CI > 30%. Safety was assessed in all patients; AEs presented by preferred term. Results: 127 pts whose immediate prior tx was CDKi + AI were enrolled, of whom 121 had centrally confirmed PIK3CA mut; median follow-up was 11.7 mo. Primary endpoint was met: proportion of pts without disease progression at 6 mo was 50.4% (95% CI, 41.2-59.6). Most frequent all-grade AEs were diarrhea (60%), hyperglycemia (58%), nausea (46%), fatigue (29%), decreased appetite (28%), and rash (28%). Most frequent grade ≥3 AEs included hyperglycemia (28%), rash (9%), and rash maculopapular (9%). Incidence of AEs leading to discontinuation was low; most frequent AEs leading to discontinuation were rash (5 pts, 3.9%), colitis, hyperglycemia, urticaria, and vomiting (2 pts, 1.6% each). Conclusions: With follow-up still ongoing, BYLieve shows in a large number of pts that ALP + FUL demonstrates clinically meaningful efficacy and manageable toxicity post CDKi tx. Building on findings from SOLAR-1, BYLieve further supports use of ALP + FUL for HR+, HER2– PIK3CA-mut ABC. Clinical trial information: NCT03056755 .

e13048 Background: Neutropenia is the most common adverse event following administration of CDK4/6 inhibitors RIB and PAL for hormone receptor–positive (HR+) MBC. There are limited comparative real-world data on TE neutropenia in pts receiving these agents. Here we report incidence, duration, and severity data on TE neutropenia in such pts from an electronic health record dataset and administrative claims. Methods: This retrospective study comprised 2 mutually exclusive cohorts of pts with MBC receiving RIB or PAL. Pts were matched 1:1 based on age and year of treatment start. Prior baseline activity of ≥6 mo was required. The MarketScan claims databases was used to evaluate incidence rates of TE neutropenia from Jan 1, 2015, to Dec 31, 2018, in pts receiving RIB or PAL. Rate ratio was calculated using a Poisson model. Data on neutropenia severity and duration were obtained from Optum de-identified Electronic Health Record dataset. Neutropenia severity was defined by neutrophil counts from lab tests (grade 1/2, 1000- < 1500/μL; grade 3, 500- < 1000/μL; grade 4 < 500/μL) within the first 180 days of treatment. Neutropenia duration was estimated using Kaplan-Meier analysis and defined as the time between first abnormal neutrophil result and a lab result demonstrating neutropenia resolution. Results: After 1:1 matching, 152 pts from the MarketScan database were included in both the PAL and RIB cohorts; 168 matched pts were included from the Optum dataset. Neutropenia was reported in 38 pts (25%) in the PAL group and 25 pts (17%) in the RIB group. The rate of neutropenia per person–treatment year was 0.5 (95% CI, 0.4-0.7) in PAL pts vs 0.4 (95% CI, 0.3-0.6) in RIB pts. The rate ratio of neutropenia between treatments (PAL vs RIB) was 1.4 (95% CI, 0.8-2.3), which was not statistically significant, likely due to small sample size. Rates of neutropenia by severity with PAL vs RIB were 32% vs 32% for grade 1/2, 35% vs 26% for grade 3, and 4% vs 4% for grade 4, respectively. The rate ratio for grade 3 or grade 4 neutropenia (PAL vs RIB) was 1.3 (95% CI, 0.9-1.8). Median neutropenia duration was 29 vs 20 days ( P< .01) with PAL vs RIB. Conclusions: Treatment of HR+ MBC with RIB and PAL requires optimal management of TE neutropenia. Real-world data showed that pts with MBC receiving PAL had a numerically higher rate of neutropenia than pts receiving RIB. Rates of grade 3 neutropenia were higher with PAL vs RIB, and duration of neutropenia was longer with PAL vs RIB. Economic burden analyses of neutropenia will be presented.

Background We performed a pooled analysis of Asian pts in the phase III MONALEESA (ML) trials, which tested ET ± RIB in pts with hormone receptor–positive/human epidermal growth factor receptor-2–negative advanced breast cancer. Methods ML-2 and ML-3 enrolled postmenopausal pts; ML-7 enrolled pre/perimenopausal pts. To pool a homogenous population and reflect health authority recommended treatment, this analysis included all pts from ML-2, first-line pts from ML-3 and pts treated with a nonsteroidal aromatase inhibitor from ML-7. Results Pts were assigned to ET + PBO (118 Asian; 562 non-Asian) or ET + RIB (136 Asian; 651 non-Asian). In Asian pts, median PFS was 12.7 mo (95% CI, 9.1-15.6) with PBO vs not reached (NR; 95% CI, 16.6-NR) with RIB (hazard ratio [HR], 0.49 [95% CI, 0.34-0.70]). In non-Asian pts, median PFS was 16.5 mo (95% CI, 14.5-18.2) with PBO vs 25.3 mo (95% CI, 23.8-27.7) with RIB (HR, 0.59 [95% CI, 0.50-0.69]). In 182 Asian pts with visceral mets, median PFS was 12.7 mo (95% CI, 8.8-16.0) with PBO vs 23.9 mo (95% CI, 14.8-NR) with RIB (HR, 0.54 [95% CI, 0.36-0.82]). In 687 non-Asian pts with visceral mets, median PFS was 13.0 mo (95% CI, 11.1-14.9) with PBO vs 23.9 mo (95% CI, 19.9-29.6) with RIB (HR, 0.55; 95% CI, 0.44-0.68). In Asian pts, overall response rate (ORR) was 33.1% (95% CI, 24.6-41.5) with PBO vs 49.3% (95% CI, 40.9-57.7) with RIB (P = 0.005). In non-Asian pts, ORR was 27.8% (95% CI, 24.1-31.5) with PBO vs 38.2% (95% CI, 34.5-42.0) with RIB (P Conclusions Significant improvements in PFS and ORR were observed in Asian pts with RIB vs PBO. Discontinuation rates due to AEs were lower in Asian pts. Clinical trial identification NCT01958021; NCT02422615; NCT02278120. Legal entity responsible for the study Novartis Pharmaceutical Corporation. Funding Novartis Pharmaceutical Corporation. Disclosure S-A. Im: Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eisai. Y-S. Yap: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: Eisai; Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Roche. K.S. Lee: Advisory / Consultancy: Lily; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Research grant / Funding (self): Dong-A Socio. L.M. Tseng: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Roche Pharma AG; Research grant / Funding (self): MSD; Travel / Accommodation / Expenses: GlaxoSmithKline. S.C. Lee: Honoraria (self): ACT Genomics; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Eisai; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Research grant / Funding (self): Taiho Pharmaceutical; Travel / Accommodation / Expenses: Amgen. Y.H. Park: Honoraria (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Eisai. I. Gounaris: Non-remunerated activity/ies: PharmaMar; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. M. Sondhi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. A. Ridolfi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. J.P. Zarate: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. Y-S. Lu: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Clinical trial study fee; Grant for clinical study for ESR1 mutation detected by cell free DNA;: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (self): Roche; Research grant / Funding (self): Merck Sharp & Dohme; Research grant / Funding (self): GlaxoSmithKline. All other authors have declared no conflicts of interest.

Background RIB plus an NSAI is indicated for premenopausal pts with hormone-receptor–positive (HR+), HER2− ABC based on data from the ML-7 trial (NCT02278120), including progression-free survival (PFS), which was longer with RIB vs PBO (median 23.8 vs 13.0 months; HR 0.55; P Methods Pre/perimenopausal pts with HR+/HER2− ABC, ≤ 1 line of prior chemotherapy, and no prior endocrine therapy for ABC were randomized 1:1 to receive RIB or PBO plus goserelin with either an NSAI (letrozole or anastrozole) or tamoxifen. The primary endpoint was PFS. OS, the key secondary endpoint, was evaluated by stratified log-rank test in the overall population and summarized using Kaplan-Meier methods. Time to 10% deterioration (TTD) was estimated using the EORTC QLQ-C30 patient questionnaire and a stratified log-rank test. Results The NSAI cohort included 248 pts in the RIB arm and 247 in the PBO arm. As of the data cutoff, 37.1% of patients in the RIB arm and 18.6% of pts in the PBO arm remained on treatment. Of the pts who discontinued study treatment, 69.2% in the RIB arm and 73.1% in the PBO arm started subsequent therapy. Median OS was not reached in the RIB arm vs 40.7 months in the PBO arm (hazard ratio, 0.699 [95% CI, 0.501-0.976]), and the benefit of adding RIB was generally consistent across pt subgroups within this cohort. Median TTD in global QoL was 34.2 months in the RIB arm vs 23.3 months in the PBO arm (hazard ratio, 0.69 [95% CI, 0.52-0.91]). Analyses of key QoL domains will be presented at the meeting. Updated analyses of adverse events revealed no unexpected safety signals. Conclusions RIB plus an NSAI prolonged OS and improved QoL vs PBO plus an NSAI in premenopausal pts with HR+, HER2– ABC. Additional follow-up did not reveal any new safety signals in this subgroup. Clinical trial identification NCT02278120. Editorial acknowledgement John McGuire, PhD, of MediTech Media, LLC funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure Y. Lu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Clinical trial study fee, grant, advisory board, speaker: Novartis; Advisory / Consultancy, Consultation fee: Pfizer; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (self): Roche; Research grant / Funding (self): Merck Sharp & Dohme; Research grant / Funding (self): Pfizer; Research grant / Funding (self): GlaxoSmithKline. A. Bardia: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Radius Health; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Immunomedics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Innocrin; Advisory / Consultancy: Biothernostics Inc.; Advisory / Consultancy, Travel / Accommodation / Expenses: Spectrum Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Taiho; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Daiichi Pharma. R.V. Vazquez: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche. M.A. Colleoni: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Honoraria (self): Novartis; Advisory / Consultancy: OBI Pharma; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Celldex. D. Tripathy: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer. B.R. Lanoue: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. D. Chandiwana: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. A. Ridolfi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. G. Hughes: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. J.P. Zarate: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. I. Gounaris: Non-remunerated activity/ies: PharmaMar; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. N. Harbeck: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer. All other authors have declared no conflicts of interest.

Background CDK4/6 inhibitor Ribociclib (RIBO) was approved by Health Canada in combination with letrozole (LET) for the treatment of HR+, HER2– advanced breast cancer (ABC) in postmenopausal women with no prior therapy for advanced disease. This was based on the significantly prolonged PFS versus placebo + LET observed in the phase 3 MONALEESA-2 trial. (NCT01958021) Here, we report the interim results for the Canadian patients (pts) enrolled in CompLEEment-1 (C-1), an open-label, phase 3b trial evaluating RIBO+LET as first-line therapy in an expanded patient population including pre-menopausal women as well as men. Methods Canadian pts with HR+, HER2- ABC, allowed to have received ≤1 line of prior chemotherapy and no prior endocrine therapy (ET) for ABC received RIBO+LET. Treatment regimen and study endpoints have been previously reported (De Laurentiis et al. ASCO 2018. Poster 1056). Results Overall, 251 Canadian pts enrolled in C-1 (N = 3255pts) were evaluated in this interim analysis (cut-off date, August 8, 2018). Median duration of exposure was 8.1 months (min; 0.0; max, 22.4). At the time of cut-off 63.3% of patients were still on treatment with the main reason for discontinuation progressive disease. Summary of demographic and baseline characteristics as well as interim efficacy and safety results are shown in Table. Most common grade ≥3 AEs were neutropenia (37.5 %), diarrhoea (2.8%) and fatigue (1.2%). Further details on the clinical impact of adverse events on treatment (i.e. action taken such as dose reductions, interruptions, etc) will be compared to the overall patient population and presented. Table . 337P (N = 251) Patients treated, n (%) Treated Treatment ongoing Discontinued N/A 251 (100) 159 (63.3) 92 (36.7) Main reasons for d/c PD Treatment related AE Other N/A 41 (16.3) 23 (9.2) 22 (8.8) Median age, y 58.0 Age category 200 (79.7); 51 (20.3) Postmenopausal, %; Pre/peri-menopausal, n (%) 189 (75.3):62 (24.7) ECOG PS 0/1/2, n (%) 125 (49.8)/115 (45.8)/11 (4.4) Disease History Extent of metastatic disease, n (%) Bone Bone only CNS Visceral Lung Liver Other N/A 190 (75.7) 53 (21.1) 4 (1.6) 167 (66.5) 118 (47.0) 65 (25.9) 41 (16.3) Number of metastatic sites, % 0-2 3-5+ Disease free interval, n (%) De novo Non de novo ≤12 months; >12 months N/A 131 (52.2) 120 (47.8) N/A 58 (23.1) 192 (76.5) 34 (13.5); 158 (63) Best overall response, n (%) CR PR Non-CR/Non-PD SD PD 1 (0.4) 52 (20.7) 89 (35.5) 63 (25.1) 12 (4.8) ORR, n (%); CBR, n (%) 53 (21.1); 166 (66.1) Clinical impact of AEs Dose reduced due to: Neutropenia Alanine aminotransferase increased Aspartate aminotransferase increased N/A 34 (13.5) 6 (2.4) 2 (0.8) Treatment related SAE, % 12 (4.8) Treatment related AE leading to d/c, % 23 (9.2) Conclusions Canadian pts represent a diverse population. Interim safety and efficacy results are generally consistent with the overall study: response rate - 21.1% for Canada v.s. 20.5% overall; clinical benefit rate - 66.1% Canada v.s 66.1% Overall, safety results were consistent with those observed in RIBO pivotal studies and no new safety signals were observed. Clinical trial identification NCT02941926. Legal entity responsible for the study Novartis. Funding Novartis. Disclosure C. Ferrario: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self): Astellas Pharma; Advisory / Consultancy: Genomic Health; Research grant / Funding (self): Amgen; Research grant / Funding (institution): Casadian therapeutics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Zymeworks. A.A. Joy: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Teva; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Genomic health; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS. S.F. Dent: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.

1056Background: CDK4/6 inhibitor RIBO has been approved for use in combination with LET for the treatment of HR+, HER2– ABC in postmenopausal women with no prior therapy for advanced disease, based...

In Latin America (LA), miscegenation of populations of Mediterranean and African ancestry has occurred for several centuries, thus facilitating the spread of hemoglobin variants. The prevalence of thalassemias, sickle-cell disease (SCD) and other hemoglobinopathies, as well as of myelodysplastic syndromes (MDS) and other diseases associated with TH is largely unknown in LA. As a retrospective registry of pts with TH in LA, the RELATH Study provides a unique opportunity to gain insight about the prevalence of TH and the patterns of care for these pts in LA. Participating countries include Brazil, Colombia, Mexico, Peru, and Venezuela. Target accrual is approximately 1,000 patients. Cases are accrued by large-volume, tertiary-care hematology centers located in large cities through a CRF designed for the study. Treatment and pt evaluation are not influenced by the study. Eligible pts have age >2 yr, consultation in the participating institutions at least once since 01/04, any disorder requiring chronic red-blood-cell (RBC) transfusion, receipt of >9 RBC units, at least one value of serum ferritin >1000 mcg/L, and/or a liver iron content (LIC) >2 mg/g dry weight (pts. with leukemia are excluded). Between Jan/06 and May/07, 239 pts have been accrued, 236 of which are evaluable. The mean age was 29.2 +/− 20.4 (range, 2 to 92), and 53.8% of pts were female. Ethnic distribution was Hispanic (41.0%), African (34.6%), and Caucasian ancestry (24.4%). The most frequent diagnoses were SCD (43.6%), beta-thalassemia major (17.4%), aplastic anemia (13.6%), and MDS (7.2%, 53.3% of which had refractory anemia). RBC transfusion was > 9 in 100% and >19 in 89.8% of pts, and mean ferritin was 2564 +/− 1834 mcg/L. LIC determination was not available or not done in 90.6% of cases. The level of hemoglobin at which transfusion was indicated was 7 to 10 g/dL in 60.7%, and 6 g/dL or less in 38.1% (N/A in 1.3%). The mean number of transfusions received was 12.2 +/− 8.8/yr (range, 1 to 80). Iron overload was assessed using ferritin (93.2%), and TH related complications were evaluated with echocardiogram (42.8%), and liver US (27.5%). TH-related complications were reported in 82.2% of cases (66.5% of pts had hepatic complications, 32.6% endocrine, 16.1% cardiac). Iron-chelation therapy was given to 39.8% of pts, more frequently on the basis of ferritin (27.5%), number of transfusions (18.2%), and complication from iron overload (5.5%). Deferoxamine (93.6%) and deferasirox (6.4%) were the most frequent chelators. In most cases, treatment was still ongoing, but reasons for discontinuation were pt refusal (4.7%), drug no longer available (4.2%), and poor compliance (3.8%). In conclusion, this preliminary report from the ongoing RELATH study shows that a registry is feasible and may provide valuable information regarding TH in various countries of LA. In addition, the study suggests so far that most LA patients undergoing chronic transfusion develop TH, whose complications could be prevented by more effective use of iron chelation, which was relatively low in this sample.