Letrozole In Postmenopausal Women Research Articles

AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer

BackgroundWindow-of-opportunity (WOO) studies provide insights into the clinical activity of new drugs in breast cancer.MethodsAMEERA-4 (NCT04191382) was a WOO study undertaken to compare the pharmacodynamic effects of amcenestrant, a selective estrogen receptor degrader, with those of letrozole in postmenopausal women with newly diagnosed, operable estrogen receptor–positive, human epidermal growth factor receptor 2−negative (ER+/HER2−) breast cancer. Women were randomized (1:1:1) to receive amcenestrant 400 mg, amcenestrant 200 mg, or letrozole 2.5 mg once daily for 14 days before breast surgery. The primary endpoint was change in Ki67 between baseline and Day 15 (i.e., day of surgery).ResultsEnrollment was stopped early because of slow recruitment, in the context of the COVID-19 pandemic. The modified intent-to-treat population consisted of 95 study participants with baseline and post-treatment Ki67 values, whereas the safety population included 104 participants who had received at least one dose of study medication. Relative change from baseline in Ki67 was − 75.9% (95% confidence interval [CI] − 81.9 to − 67.9) for amcenestrant 400 mg, − 68.2% (− 75.7 to − 58.4) for amcenestrant 200 mg, and − 77.7% (− 83.4 to − 70.0) for letrozole (geometric least-squares mean [LSM] estimates). Absolute change in ER H-score from baseline (LSM estimate) was − 176.7 in the amcenestrant 400 mg arm, − 202.9 in the amcenestrant 200 mg arm, and − 32.5 in the letrozole arm. There were no Grade ≥ 3 treatment-related adverse events.ConclusionsBoth amcenestrant and letrozole demonstrated antiproliferative activity in postmenopausal women with previously untreated, operable ER+/HER2− breast cancer and had good overall tolerability.Trial RegistrationClinicalTrials.gov, NCT04191382 https://clinicaltrials.gov/ct2/show/NCT04191382. Registered 9 December 2019.

Expanded Access Study of Palbociclib Plus Letrozole for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer in Latin America for Whom Letrozole Therapy is Deemed Appropriate.

Palbociclib is a cyclin-dependent kinase 4/6 inhibitor that is approved in the United States for the treatment of hormone receptor‒positive (HR+)/human epidermal growth factor receptor‒2 negative (HER2-) advanced breast cancer (ABC). The objectives of this expanded access trial were to provide palbociclib in combination with letrozole to patients with HR+/HER2- ABC in Argentina, Brazil, Colombia, and Mexico who were candidates for letrozole therapy before commercial availability of palbociclib, and to evaluate the safety and tolerability of palbociclib plus letrozole. Postmenopausal women aged ≥18 years with HR+/HER2- ABC were eligible to participate in this study. Patients received palbociclib 125 mg once daily (3/1 schedule) and letrozole 2.5 mg once daily (continuous schedule). Safety, objective response rate (ORR), and duration of treatment were evaluated. A total of 130 patients were treated with palbociclib plus letrozole (Argentina, n = 33; Brazil, n = 35; Colombia, n = 28; Mexico, n = 34). The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (70.0%), leukopenia (34.6%), anemia (33.8%), decreased neutrophil count (27.7%), and thrombocytopenia (24.6%); 22.3% of patients required a palbociclib dose reduction due to adverse events (AEs). Serious AEs were reported in 32 patients (24.6%). The ORR was 24.8% (95% confidence interval 17.6‒33.2), and the median duration of treatment was 10.6 months (range 0.1‒29.3). Palbociclib in combination with letrozole was generally well tolerated with a clinically manageable safety profile; the observed ORR supported treatment benefit in Latin American women with HR+/HER2- ABC. ClinicalTrials.gov, NCT02600923.

Abstract P2-12-02: Efficacy, safety and survival of neoadjuvant chemotherapy with different estrogen deprivation stratified by menstrual status versus chemotherapy alone in locally advanced breast cancer (SHPD002)—— A randomized multicentre, open-label, phase 3 Triab

Abstract BackgroundAchieving pathologic complete response (pCR) because of neoadjuvant therapy has been correlated with long-term clinical benefit, however, luminal-like tumors achieve a lower rate of pCR in comparison with other subtypes. The Shanghai Pudong (SHPD) 002 trial compares neoadjuvant chemotherapy concurrently with or with different estrogen deprivation therapy separately in premenopausal and postmenopausal patients with locally advanced breast cancer. MethodsIn this prospective, multicentre, neoadjuvant, phase III trial, 236 patients with locally advanced breast cancer were randomly assigned (2:1) to receive neoadjuvant chemotherapy (NCT) with gonadotropin-releasing hormone agonist (GnRHa) in premenopausal women or letrozole in postmenopausal women compared with chemotherapy alone. The primary endpoint was pCR (ypT0/is/ypN0). Secondary endpoints included disease-free survival, overall survival, and safety. This trial is registered with ClinicalTrials.gov, number NCT NCT02221999.Results A total of 236 patients were included. pCR was achieved by 20.4% in the chemotherapy plus ET group and 38.6% in the chemotherapy group. In postmenopausal patients, pCR was observed in 22.6% when treated with letrozole, 32.4% with NCT alone (p=0.276). Premenopausal patients with NCT and GnRHa achieved a significantly lower pCR of 18.8% than those of 42.9% in patients with NCT alone(p=0.003). A posthoc analysis showed CPS+EG score 0-3 was significantly more probable in patients with GnRHa (OR, 0.245; 95% CI, 0.072 to 0.832, P=0.024) than in those without GnRHa in the premenopausal patients who didn’t achieve near-pCR. After a median follow-up of 45 months, there was no significant difference concerning disease-free survival (DFS) (p=0.874) or overall survival (OS) (P =0.947) between the 2 postmenopausal groups. GnRHas significantly improved survival outcome in premenopausal patients (3-year OS, 100% with GnRHas, vs 88.2% without; log-rank p=0.034). Improved DFS (log-rank p = 0.001) and OS (log-rank p=0.003) were strongly associated with pCPS+EG score and GnRHa usage in premenopausal patients.ConclusionsConcurrent administration of GnRHas during neoadjuvant chemotherapy improves OS in premenopausal patients, though it does not increase the pCR rate. The adoption of the CPS+EG score may be a better surrogate endpoint for survival outcomes. The addition of letrozole to neoadjuvant chemotherapy confers no therapeutic advantage in terms of tumor response or survival outcome. Citation Format: Liheng Zhou, Shuguang Xu, Xiaohong Xue, Yinzhou Zhang, Bei Gu, Baoxing Lin, Junwen Bai, Hongwei Zhang, Kejin Wu, Yanping Lin, Yumei Ye, Yueyao Du, Xiaonan Sheng, Yaqian Xu, Jie Zhang, Wenjin Yin, Jinsong Lu. Efficacy, safety and survival of neoadjuvant chemotherapy with different estrogen deprivation stratified by menstrual status versus chemotherapy alone in locally advanced breast cancer (SHPD002)—— A randomized multicentre, open-label, phase 3 Triab [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 P2-12-02.

Abstract PD15-05: Assessment of estrogen receptor (ESR1) mRNA expression for prediction of extended aromatase inhibitor benefit in HR-positive breast cancer using NRG Oncology/NSABP B-42

Abstract Background: In NSABP B-14, the quantitative levels of ESR1 mRNA, assessed using the standardized 21-gene assay and qRT-PCR platform predicted tamoxifen benefit (interaction p-value <0.001). NSABP B-42 evaluated the effect of extended letrozole in postmenopausal women with hormone receptor-positive breast cancer who have completed 5 years of hormonal therapy with either an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor. We proposed to determine if ESR1 mRNA, reported as the quantitative ER single gene score, is predictive of the magnitude of benefit from extended adjuvant endocrine therapy with letrozole in patients enrolled in NSABP B-42. Methods: This prospectively planned retrospective study used a stratified cohort sample drawn from the 2,589 B-42 patients with available tumor tissue blocks and appropriate consent. All 133 patients who experienced distant recurrence and 48 patients who experienced local/regional but not distant recurrence were included along with a stratified random sample of 547/2,408 patients without recurrence. The primary endpoint was distant recurrence. The primary analysis tested for the interaction between the continuous ER single gene score and the effect of extended letrozole treatment using a weighted Cox proportional hazards regression model. A secondary analysis considered the ER single gene score categorized using the prespecified cutoff of ≤9.1 versus >9.1. Recurrence-free interval was a secondary endpoint. Results: The results of the assay were available for 587 patients. The median ER score was 10.2 (IQR 9.3-11.0). There were 131 patients (23.2% weighted) with ER ≤9.1 and 456 (76.8% weighted) with ER >9.1. No significant interaction of the effect of extended letrozole treatment was found for either the ER single gene score (interaction hazard ratio letrozole vs. placebo with an IQR change in ER score 1.10, 95% CI 0.66 - 1.82, p=.72) or the categories ER ≤9.1 (treatment HR=0.40, 95% CI 0.15-1.06) or ER >9.1 (treatment HR=0.70, 95% CI 0.43-1.12) (interaction p=.32). There was also no apparent prognostic effect of the ER single gene score for distant recurrence with placebo treatment after 5 years of endocrine therapy (p=.12). Results were similar in analyses of any recurrence, analyses adjusting for the proliferation axis from the 21-gene assay, and subgroup analyses by nodal and HER2-status. Conclusions: The B-42 study provided no evidence that ESR1 mRNA as measured by the ER single gene score can inform decisions regarding extended letrozole therapy after 5 years of adjuvant endocrine therapy. Confidence intervals were relatively wide but rule out a strong predictive effect of the ER single gene score in the expected direction. Support: U10CA180868, -180822, U24CA196067; Novartis; Exact Sciences Citation Format: Eleftherios Mamounas, Hanna Bandos, Priya Rastogi, Michael R Crager, Carolyn Mies, Peter C Lucas, Charles E Geyer, Jr, Louis Fehrenbacher, Mark L Graham, Stephen KL Chia, Adam M Brufsky, Janice M Walshe, Gamini S Soori, Shaker R Dakhil, Soonmyung Paik, Sandra M Swain, Frederick L Baehner, Steven Shak, Norman Wolmark. Assessment of estrogen receptor (ESR1) mRNA expression for prediction of extended aromatase inhibitor benefit in HR-positive breast cancer using NRG Oncology/NSABP B-42 [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 PD15-05.

Abstract 336: Gut microbiome predicts response to CDK4/6 inhibitor and immune check point inhibitor combination in patients with hormone receptor positive metastatic breast cancer

Abstract Background: CDK4/6 inhibitors (CDK4/6i) have been shown to modulate immune responses in the preclinical setting. Palbociclib is a front-line therapy for hormone receptor positive (HR+) metastatic breast cancer (MBC), and the combination with immune check point inhibitors (ICI) is increasingly being studied. An ongoing phase I trial was designed to test the safety and efficacy of palbociclib, pembrolizumab, and letrozole in postmenopausal women with HR+ HER2- MBC (NCT02778685). Stool microbiome was collected and analyzed. The aim of this study is to determine the association of gut microbiota and response using metagenome sequencing data through a machine learning model. Methods: Postmenopausal women with histologically proven stage IV HR+ HER2- MBC were enrolled. Stool samples were collected at baseline and during treatment for analysis using metagenome sequencing. Response per RECIST 1.1 were grouped into: responders (complete response or partial response) and non-responders (stable disease or progressive disease). Using metagenomic relative abundance data, a gradient-boosted tree model was developed with leave-one-patient-out cross validations to predict patient response at baseline. Kruskal-Wallis tests were used to assess the differences of the most important microbiota relative abundance (generated from the machine learning model) between responders and non-responders. Results: Forty-seven stool samples from 11 patients were collected at baseline and during treatment, and metagenome sequencing was performed. For predictive modeling, the validation Area Under the Receiver Operating Characteristic Curve (AUROC) and Area Under the Precision Recall Curve (AUPRC) were 0.71 and 0.83, respectively. Among the top 5 features from the model, patients with a larger relative abundance of Gemmiger formicillis have increased probability of responding to therapy (p<0.05 uncorrected), whereas an increase of Bacteroides vulgatus have reduced probability of responding to therapy (p<0.05 uncorrected). The relative abundance of Gemmiger formicillis at baseline has been reported in recent studies to be higher in patients with long term benefit (Aarnoutse et al. 2017). Thus, there is increasing evidence that gut microbiota plays a role in the pathogenesis of breast cancer and response of MBC patients to systemic cancer therapy. Citation Format: Chi Wah Wong, Susan E. Yost, Jin Sun Lee, Sarah K. Highlander, Yuan Yuan. Gut microbiome predicts response to CDK4/6 inhibitor and immune check point inhibitor combination in patients with hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 336.

Abstract OT-09-11: AMEERA-4, a phase 2 window study of SAR439859 vs letrozole in post-menopausal women with newly diagnosed estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer

Abstract Background Endocrine therapy targeting estrogen receptor (ER) signaling is the standard of care for women with ER+ breast cancer. Selective ER degraders (SERDs) block ER signaling through dual competitive antagonism and receptor degradation. SAR439859, a potent, oral SERD, is in clinical development for ER+/HER- breast cancer. AMEERA-4 (NCT04191382; ACT16106) is a 14-day preoperative, non-therapeutic ‘window of opportunity’ trial to assess the direct effects of SAR439859 on tumor cell proliferation by evaluating the pharmacodynamic activity of SAR439859 in ER+/HER2- breast cancer. Methods This international, open-label, Phase 2 randomized study evaluates SAR439859 at two dose levels vs the aromatase inhibitor letrozole by assigning 126 preoperative patients 1:1:1 to receive SAR439859 400 mg/day, SAR439859 200 mg/day or letrozole 2.5 mg/day. SAR439859 dosing is based on an ongoing AMEERA-1 Phase 1/2 study (NCT03284957; TED14856) in metastatic breast cancer. Postmenopausal women with ER+/HER2- breast cancer indicated for immediate surgery (Stage I, Stage II or operable Stage III), Eastern Cooperative Oncology Group performance status 0-1, and Ki67 levels of ≥ 15% are eligible. Exclusion criteria include disorders potentially affecting absorption of SAR439859 or letrozole, and any prior therapy for breast cancer. Patients receive study treatment for 14 days, with the last dose given on the day before surgery. Paired tumor biopsies for assessment of biomarkers are performed at baseline and during surgery. The primary study endpoint is change in Ki67, a predictor of treatment benefit and long-term survival outcomes, after 14 days of treatment compared with baseline. Secondary endpoints include proportion of patients with ≥ 50% decrease in Ki67, ER expression to assess degradation, and safety. Pharmacokinetics of SAR439859, additional tumor markers, genomic mutation profile, Preoperative Endocrine Prognostic Index and pathological complete response will also be assessed. The study is currently recruiting. Funding: Sanofi. © 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved. Citation Format: Mario Campone, Christina Herold, Qiuyan Wang, Vasiliki Pelekanou, Sylvaine Cartot-Cotton, Bethany Ling. AMEERA-4, a phase 2 window study of SAR439859 vs letrozole in post-menopausal women with newly diagnosed estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer [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 OT-09-11.

Phase II preoperative window study of SAR439859 versus letrozole in post-menopausal women with newly diagnosed estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

TPS1108 Background: Endocrine therapy targeting ER signaling is the standard of care for women with ER+ breast cancer. Selective ER degraders (SERDs) block ER signaling through dual competitive antagonism and receptor degradation. SAR439859, a potent, oral SERD, is in clinical development for ER+/HER2- breast cancer. This study is a 14-day preoperative non-therapeutic ‘window of opportunity’ trial to assess the direct effects of SAR439859 on tumor cell proliferation by evaluating the pharmacodynamic activity of SAR439859 in ER+/HER2- breast cancer. Methods: This international, open-label, Phase II randomized study (NCT04191382; ACT16106) evaluates SAR439859 at two dose levels versus the aromatase inhibitor letrozole by assigning 126 preoperative patients 1:1:1 to receive SAR439859 400 mg/day, SAR439859 200 mg/day or letrozole 2.5 mg/day. SAR439859 dosing is based on an ongoing Phase I/II study (NCT03284957; TED14856) in metastatic breast cancer (Campone. SABCS 2019. P5-11-02). Postmenopausal women with ER+/HER2- breast cancer indicated for immediate surgery (Stage I, Stage II or operable Stage III), Eastern Cooperative Oncology Group performance status 0–1 and Ki67 levels of ≥ 15% are eligible. Exclusion criteria include disorders potentially affecting absorption of SAR439859 or letrozole, and any prior therapy for breast cancer. Patients receive study treatment for 14 days, with the last dose given on the day before surgery. Paired tumor biopsies for assessment of biomarkers are performed at baseline and during surgery. The primary study endpoint is change in Ki67, a predictor of treatment benefit and long-term survival outcomes, after 14 days of treatment compared with baseline. Secondary endpoints include proportion of patients with ≥ 50% decrease in Ki67, ER expression to assess degradation, and safety. Pharmacokinetics of SAR439859, additional tumor markers, genomic mutation profile, Preoperative Endocrine Prognostic Index and pathological Complete Response will also be assessed. The study is currently recruiting; target enrollment: n = 126. Clinical trial information: NCT04191382 .

Abstract P5-12-01: SOLE (study of letrozole extension), a phase 3 randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC): Final analysis and sole estrogen substudy (SOLE-EST)

Abstract Background: In animal models of hormone receptor positive (HR+) breast cancer, acquired resistance to continued letrozole was shown to be reversed by estrogen-induced apoptosis. We hypothesized that the rise in estrogen levels during short treatment interruptions would resensitize breast cancer cells to letrozole and improve treatment outcome. SOLE tested the hypothesis that 3 mos treatment-free intervals during extended adjuvant therapy will improve disease-free survival (DFS). We previously reported the primary endpoint after 60 mos median follow-up: extended intermittent letrozole did not improve DFS vs extended continuous letrozole. However, only 9% of pts had breast cancer events, justifying updating the analysis with longer follow-up. The dynamic of recovery of estrogen levels after stopping letrozole therapy has not been previously reported. Methods: SOLE enrolled 4884 postmenopausal women with HR+ lymph node-positive BC who had completed 4-6 yrs of adjuvant endocrine therapy (19% SERM, 43% AI, 38% both; stratification factor). Pts were randomized to an additional 5 yrs continuous letrozole (2.5 mg daily; n=2441) vs 5 yrs intermittent letrozole (taken for the first 9 mos of yrs 1-4, and 12 mos in yr 5; n=2443). We report the final analysis of the SOLE trial after 84 mos median follow-up. In SOLE-EST, levels of estradiol (E2), estrone (E1) and estrone sulphate (E1S) at 0, 9, 10.5 and 12 mos after randomization were determined using a highly sensitive assay in a subgroup of 90 evaluable patients (21 in the continuous and 69 in the intermittent group). Results: There were 923 DFS events. 7 yr DFS was 81.5% in both groups. More pts had distant metastases in the continuous group (8.7% vs 7.5%) while second (non-breast) malignancies were more frequent in the intermittent group (5.5% vs 4.7%). Similar outcomes were observed for breast cancer-free interval (BCFI) (88.6% vs 88.0%), distant recurrence-free interval (DRFI) (91.6% vs 90.4%), and overall survival (OS) (90.6% vs 89.6%) for pts assigned intermittent vs continuous letrozole. In the intermittent group, median E2, E1 and E1S levels more than doubled compared with levels at 9 mos after randomization in the first 6 weeks after stopping letrozole during the treatment free interval while levels were stable for the 21 pts tested in the continuous group. Conclusions: Among postmenopausal women with HR+ BC, extended intermittent letrozole did not improve DFS vs continuous letrozole. Similar outcome was consistently observed for BCFI, DRFI and OS. The SOLE-EST substudy indicates an important increase in estrogen levels as soon as 6 weeks after stopping letrozole therapy in the intermittent group. Further investigation of prior exposure to aromatase inhibitors in relation with outcome and with E2, E1 and E1S levels in SOLE-EST are underway. Citation Format: Guy Jerusalem, Subrina Farah, Jacquie Chirgwin, Stefan Aebi, Per Karlsson, Patrick Neven, Erika Hitre, Marie-Pascale Graas, Edda Simoncini, Claus Kamby, Alastair Thompson, Sibylle Loibl, Joaquín Gavilá, Katsumasa Kuroi, Christian Marth, Bettina Müller, Seamus O'Reilly, Andrea Gombos, Thomas Ruhstaller, Harold Burstein, Manuela Rabaglio, Barbara Ruepp, Giuseppe Viale, Richard D Gelber, Alan S Coates, Angelo Di Leo, Aron Goldhirsch, Meredith Regan, Marco Colleoni. SOLE (study of letrozole extension), a phase 3 randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC): Final analysis and sole estrogen substudy (SOLE-EST) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-01.

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study

BackgroundTreatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients.MethodsEvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor–positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT.ResultsOut of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment.ConclusionsDespite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process.Trial registrationClinical Trials Number: CFEM345DDE19

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial.

PALOMA-2 confirmed that first-line palbociclib + letrozole improved progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.46-0.72) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This analysis evaluated palbociclib-associated hematologic adverse events (AEs) and provides insight on managing these AEs. Postmenopausal women with ER+/HER2- ABC were randomly assigned 2:1 to letrozole (2.5 mg daily continuously) plus oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments were performed at baseline, days 1 and 15 (first two cycles) and day 1 of subsequent cycles, and included white blood cell, platelet, and absolute neutrophil count (ANC). PALOMA-2 randomized 666 women to palbociclib + letrozole (n = 444) or placebo + letrozole (n = 222). Neutropenia was the most common AE (95.3%) with palbociclib (grade 3, 55.6%; grade 4, 11.5%) and was managed by dose modifications; progression-free survival was similar between patients who experienced grade ≥ 3 neutropenia versus those who did not. Median (range) time to onset of neutropenia with palbociclib + letrozole was 15 (12-700) days (grade ≥ 3, 28.0 [12-854] days); median duration of each neutropenia episode grade ≥ 3 was 7.0 days. Asian ethnicity and low baseline ANC were associated with increased risk of grade 3/4 neutropenia with palbociclib (p < .001). Palbociclib + letrozole was generally well tolerated. Neutropenia, the most frequently reported AE in women with ER+/HER2- ABC, was mostly transient and manageable by dose modifications in patients who experienced grade ≥ 3 neutropenia, without appearing to compromise efficacy. (Pfizer; NCT01740427) IMPLICATIONS FOR PRACTICE: Palbociclib demonstrated an acceptable safety profile in PALOMA-2 in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) receiving first-line palbociclib + letrozole. Although hematologic adverse events (AEs) are typically expected with anticancer therapies and are often clinically significant, palbociclib-related hematologic AEs, particularly neutropenia (most frequent AE), were transient/manageable by dose reduction, interruption, or cycle delay, which is in contrast to the more profound neutropenia associated with chemotherapy. Palbociclib dose adjustments decreased hematologic AE severity without appearing to compromise efficacy, supporting palbociclib + letrozole as a first-line treatment for ER+/HER2- ABC.

Investigating racial differences in treatment responses through analysis of real-world data (RWD).

e18141 Background: Clinical trials remain the most reliable means to evaluate drug efficacy and safety for evidence-based cancer care. However, there is a significant racial disparity among participants in clinical trials. For example, only 1-3% of the participants in registration trials of immune checkpoint inhibitors (CPIs) in advanced non-small cell lung cancers (aNSCLCs) were Black. RWD data enable assessment of whether clinical trial results can be generalized to broader populations. Methods: We analyzed clinical records of &gt; 145,000 cancer patients treated at Mount Sinai hospitals. Therapeutic agents approved by FDA in recent years were assessed for responses across various race groups. Time to treatment discontinuation (TTD) was used as a surrogate clinical endpoint for outcomes. Results: Overall we did not observe significant differences in TTD among different race groups for the following drugs and indications we examined: palbociclib in metastatic breast cancer (mBC), EGFR tyrosine kinase inhibitors in aNSCLC, EGFR antibody cetuximab and panitumumab in metastatic colorectal cancer with wild type KRAS, abiraterone in metastatic castration-resistant prostate cancer (mCRPC), enzalutamide in mCRPC, sorafenib in unresectable hepatocellular carcinoma (HCC), CPIs in metastatic melanoma. For example, the median TTD of palbociclib in combination with fulvestrant or letrozole in post-menopausal women with HR+HER2- mBC was 181, 261, and 160 days in White (n = 114), Black (n = 55), other (n = 48) race groups, respectively (P = 0.61, log-rank test). Among patients with unresectable HCC treated with sorafenib, the median TTD was 64, 49, and 67 days in the White (n = 201), Black (n = 127) and other (n = 243) race groups, respectively (P = 0.70). However, when CPIs in aNSCLC were examined, we observed a significantly longer TTD in the Black group (median TTD not reached; n = 77) compare to the non-Black group (169 days, 95% CI 133-331; n = 211), P = 0.0049, median follow up 194 days. Conclusions: RWD showed there are no apparent differences of treatment response in various race groups for most new therapeutic agents. Preliminary results of CPIs in aNSCLC suggested a favorable response in the Black than the non-Black population.

Treatment Patterns and Outcomes Associated With Palbociclib Plus Letrozole for Postmenopausal Women With HR+/HER2− Advanced Breast Cancer Enrolled in an Expanded Access Program

PurposeTo evaluate treatment patterns and clinical outcomes of patients who received palbociclib in combination with letrozole in any line of therapy for treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer in an expanded access program (EAP) in the United States. Patients and MethodsA retrospective chart review study was conducted of patients previously enrolled in the palbociclib EAP. Complete data from time of initial diagnosis of metastatic breast cancer until date of chart abstraction were obtained. Clinical outcomes as assessed by site investigators included clinical benefit rate, progression-free survival, and overall survival. Survival was descriptively assessed using Kaplan-Meier methods. ResultsOf 238 patients enrolled in the EAP, data from 126 patients were included. Median age was 62.5 years at EAP enrollment; 25% had de novo metastatic disease. Visceral disease was present in 71% of patients. The disease of most patients was heavily pretreated; nearly 60% of patients had received 3 or more prior lines for metastatic disease before initiating palbociclib + letrozole therapy. Most patients (87%) had received prior endocrine therapy, and 68% had received prior chemotherapy for metastatic disease. Patients with prior endocrine therapy for metastatic disease had a clinical benefit rate of 30%, while those with prior chemotherapy had a 26% clinical benefit rate. Patients receiving 2 or more prior lines had 6- and 12-month progression-free survival rates of 35% and 21%, respectively, and 12- and 24-month overall survival rates of 62% and 35%, respectively. ConclusionMost patients derived benefit from palbociclib + letrozole treatment despite having received multiple prior treatment lines for metastatic disease.

Cost-effectiveness analysis of ribociclib plus letrozole versus palbociclib plus letrozole in the United Kingdom.

ObjectiveTo evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with hormone receptor positive (HR+) and human epidermal growth receptor 2 negative (HER2−) advanced breast cancer from a UK payer perspective.MethodsA cohort-based partitioned survival model was developed to evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with HR+/HER2− advanced breast cancer over a lifetime horizon. The analysis was carried out from a National Health Services and Personal Social Services perspective, and results are presented in incremental costs per quality adjusted life years. Clinical data from three randomized controlled trials (MONALEESA-2, PALOMA-1 and PALOMA-2 studies) were used, and supplemented with available real world evidence. Costs categories comprised of drug acquisition, medical management, and treatment of adverse events. Healthcare resource utilization data were identified from literature and unit costs sourced from secondary sources. Utility values were derived from MONALEESA-2 study and were supported with values identified from literature. Both deterministic and probabilistic analyses were carried out to assess uncertainty.ResultsIn the base case, treatment with ribociclib plus letrozole increased mean progression free survival (PFS) by 4.1 months and overall survival by 5.0 months compared to palbociclib plus letrozole. Further, treatment with ribociclib plus letrozole resulted in cost-savings of £8464 and incremental QALYs of 0.261, demonstrating that treatment with ribociclib plus letrozole is dominant to treatment with palbociclib plus letrozole. The probabilistic analysis also yielded mean cost-savings of £7914 and mean QALY gain of 0.273. At willingness-to-pay threshold of £30 000 per QALY, treatment with ribociclib plus letrozole had a 92% probability of being cost-effective compared to palbociclib and letrozole.ConclusionsThe results of the analysis demonstrate that ribociclib plus letrozole treatment is both cost-saving and a cost-effective option amongst the available cyclin dependent kinase 4/6 inhibitors for the treatment of post-menopausal women with advanced breast cancer. The biggest driver of the cost savings were the lower acquisition costs of ribociclib.

Cost-effectiveness Analysis of Ribociclib plus Letrozole versus Palbociclib plus Letrozole in the United Kingdom

Objective: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with hormone receptor positive (HR+) and human epidermal growth receptor 2 negative (HER2-) advanced breast cancer from a UK payer perspective. Methods: A cohort-based partitioned survival model was developed to evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole in post-menopausal women with HR+/HER2- advanced breast cancer over a lifetime horizon. The analysis was carried out from a National Health Services and Personal Social Services perspective, and results are presented in incremental costs per quality adjusted life years. Clinical data from three randomized controlled trials (MONALEESA-2, PALOMA-1 and PALOMA-2 studies) were used, and supplemented with available real world evidence. Costs categories comprised of drug acquisition, medical management, and treatment of adverse events. Healthcare resource utilization data were identified from literature and unit costs sourced from secondary sources. Utility values were derived from MONALEESA-2 study and were supported with values identified from literature. Both deterministic and probabilistic analyses were carried out to assess uncertainty. Results: In the base case, treatment with ribociclib plus letrozole increased mean progression free survival (PFS) by 4.1 months and overall survival by 5.0 months compared to palbociclib plus letrozole. Further, treatment with ribociclib plus letrozole resulted in cost-savings of £8464 and incremental QALYs of 0.261, demonstrating that treatment with ribociclib plus letrozole is dominant to treatment with palbociclib plus letrozole. The probabilistic analysis also yielded mean cost-savings of £7914 and mean QALY gain of 0.273. At willingness-to-pay threshold of £30 000 per QALY, treatment with ribociclib plus letrozole had a 92% probability of being cost-effective compared to palbociclib and letrozole. Conclusions: The results of the analysis demonstrate that ribociclib plus letrozole treatment is both cost-saving and a cost-effective option amongst the available cyclin dependent kinase 4/6 inhibitors for the treatment of post-menopausal women with advanced breast cancer. The biggest driver of the cost savings were the lower acquisition costs of ribociclib.

Economic Evaluation of Letrozole for Early Breast Cancer in a Health Resource-Limited Setting

Objective Long-term aromatase inhibitor (AI) therapy is expected to improve the health outcomes with high health resource consumption in early breast cancer. The aim of the study was to assess the cost-effectiveness of letrozole for postmenopausal women with estrogen receptor positive early breast cancer in a health resource-limited setting. Methods A Markov model was developed to project the lifetime outcomes based on the clinical course of early breast cancer. The clinical and utility data were derived from reported results. Costs were estimated from the perspective of Chinese health care. The quality-adjusted life-year (QALY) and incremental cost-effective ratio (ICER) were measured. Probabilistic sensitivity and one-way analyses were conducted. Results Compared to 5 years of tamoxifen therapy, 5 years of AI treatment with letrozole improved the QALYs (10.44 versus 10.84) and increased the lifetime costs (CNY ¥13,613 versus CNY ¥28,797), resulting in an ICER of CNY ¥38,092 /QALY. The ICER of 5 years of letrozole versus 2–3 years of tamoxifen and then letrozole was CNY ¥68,233 /QALY. Sensitivity analyses showed that the age of initiating adjuvant endocrine therapy was the most influential parameter. Conclusions In health resource-limited settings, adjuvant endocrine therapy with letrozole is a cost-effective strategy compared to tamoxifen in women with early breast cancer.

Abstract P5-21-24: Retrospective assessment of treatment patterns and outcomes associated with palbociclib plus letrozole for postmenopausal women with HR+/HER2– advanced breast cancer enrolled in an early access program

Abstract Background: The objective of this study was to evaluate treatment patterns and clinical outcomes among patients who received palbociclib in combination with letrozole (P+L) for the treatment of HR+/HER2–advanced breast cancer (ABC) as part of an Expanded Access Program (EAP) in the United States. Methods: Data were obtained by a retrospective chart review of patients previously enrolled in the EAP. Complete data from time of initial diagnosis of ABC until the date of chart abstraction (end of follow-up), including the post-EAP period, were obtained. Clinical outcomes assessed included clinical benefit rate (CBR), defined as complete response, partial response, or stable disease for ≥24 weeks from P + L initiation, progression free survival (PFS) and overall survival (OS). Survival outcomes were assessed using the Kaplan-Meier statistical analysis. Results: Data from 126 patients were included in this analysis. Median age was 62.5 years at EAP enrollment, and a majority of patients were Caucasian (83%). Approximately 25% of patients had de novo metastatic disease. A majority of patients had a performance status of ECOG 0 (56%) or 1 (37%) at EAP enrollment. Visceral disease was present in 71% of patients and 16% had bone-only disease. The majority of patients in this cohort from the EAP were heavily pre-treated, having had up to 5 prior lines of therapy in the metastatic setting prior to initiating P + L therapy; nearly 59% received 3+ prior lines before initiating P + L. Only 11% of patients received P + L as their initial regimen for MBC. At the time of the last available record, 12 patients were still on P + L therapy, an average of 21 months after the start of the EAP program. Nearly 80% of patients had prior AI exposure and 69% had prior chemotherapy. CBR was 33% for the overall sample of patients treated with P + L and 22% in those with 3+ prior lines of treatment. Patients with prior AI exposure in the ABC setting (n=100) had a CBR of 27% while those without prior AI exposure had CBR of 58%. Patients with prior chemotherapy (n=87) had a CBR of 28% and those without prior chemotherapy had CBR of 46%. For the entire cohort, 6- and 12-month PFS rates were 40% and 25% respectively; 12- and 24-month OS rates were 66% and 44%, respectively. Patients receiving 3+ lines of prior therapy had 6- and 12-month PFS rates of 28% and 19%, respectively, and 12- and 24-month OS rates of 59% and 34% respectively. Conclusions: Our results suggest that the majority of patients enrolled in the EAP program derived benefit from receiving treatment with P + L despite multiple prior lines of treatment and prior endocrine-based therapy, including prior AI. These findings further demonstrate the benefit of treatment with palbociclib combination therapy in HR+/HER2– MBC. Citation Format: Brufsky A, Davis K, Mitra D, Nagar S, McRoy L, Cotter M, Stearns V. Retrospective assessment of treatment patterns and outcomes associated with palbociclib plus letrozole for postmenopausal women with HR+/HER2– advanced breast cancer enrolled in an early access program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-24.

Abstract P5-18-01: Extended continuous vs intermittent adjuvant letrozole in postmenopausal women with lymph node-positive, early breast cancer (IBCSG 37-05/BIG 1-07 SOLE): Impact on patient-reported symptoms and quality of life

Abstract Background: SOLE efficacy results presented at ASCO 2017 showed that extended intermittent vs continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women who had received 4-6 years of adjuvant endocrine therapy for hormone-receptor positive (HR+), lymph-node positive breast cancer. Previous studies showed that the burden by symptoms related to endocrine therapy can be substantial. Even if symptoms improve during the treatment course, extending treatment implies continuation of symptoms. We compared differences in patient-reported symptoms (PRS) and quality of life (QoL) between extended continuous and intermittent letrozole over the first two years of trial treatment. Methods: From Nov 2007 to Dec 2010, 956 postmenopausal women who were disease-free following 4-6 years of prior adjuvant endocrine therapy for HR+, node-positive breast cancer were enrolled in the QoL substudy of the randomized phase III trial SOLE at selected centers. Patients receive extended continuous letrozole (2.5 mg daily) for 5 years or intermittent letrozole, taken for the first 9 months of years 1-4, and 12 months in year 5. 955 patients completed the 18-item Breast Cancer Prevention Trial (BCPT) Symptom Scales and further symptom-specific and global QoL indicators at baseline, and at 6, 12, 18 and 24 months after randomization. Differences in change of PRS and QoL from baseline between the two administration schedules were tested at 12 and 24 months for 8 symptom scales, 4 additional symptom and 4 global QoL indicators using mixed models with repeated measures. Results: Small changes in PRS and QoL scores were observed between baseline and 12 months after randomization, i.e. at the end of the first treatment-free interval in the intermittent arm. These changes showed a consistent pattern of greater worsening for patients receiving continuous compared to patients receiving intermittent letrozole. Patients receiving continuous letrozole reported a significantly greater worsening in vaginal problems (p&amp;lt;.02), musculoskeletal pain (p&amp;lt;.03), sleep disturbance (p&amp;lt;.01), physical wellbeing (p&amp;lt;.01) and mood (p&amp;lt;.03). At 24 months (after 2nd treatment-free interval) patients with intermittent letrozole reported a greater improvement in hot flushes (p&amp;lt;.03) than those with continuous letrozole. Changes in the other outcomes did not significantly differ between arms at 24 months. Conclusion: Although changes in PRS and QoL were small, there was a consistent pattern favoring the intermittent arm. For several symptoms and global QoL indicators, significantly less worsening was observed with the intermittent administration, mainly during the first year of extended treatment, due to small improvements during the treatment-free interval. Froma QoL perspective, women who suffer from endocrine side-effects in the extended setting may benefit from an intermittent administration. Citation Format: Ribi K, Luo W, Colleoni M, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Di Lauro V, Gomez HL, Ruhstaller T, Abdi E, Di Leo A, Müller B, Maibach R, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J. Extended continuous vs intermittent adjuvant letrozole in postmenopausal women with lymph node-positive, early breast cancer (IBCSG 37-05/BIG 1-07 SOLE): Impact on patient-reported symptoms and quality of life [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-01.

Abstract P5-21-27: Efficacy and safety of ribociclib plus letrozole in US patients enrolled in the MONALEESA-2 study

Abstract Background: Endocrine-based therapy is the standard of care for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC), in whom delaying disease progression is the primary goal. In the randomized Phase 3 MONALEESA-2 study (ClinicalTrials.gov identifier, NCT01958021), first-line ribociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) + letrozole significantly prolonged progression-free survival (PFS) compared with placebo + letrozole in postmenopausal women with HR+, HER2− ABC (hazard ratio, 0.556; 95% confidence interval [CI], 0.429–0.720) at the interim analysis cutoff date. Here, we present safety and efficacy data from US patients who were enrolled in the MONALEESA-2 study. Methods: Postmenopausal women (N=668) with HR+, HER2− ABC who did not receive prior systemic treatment for ABC and had an Eastern Cooperative Oncology Group performance status score of ≤1, adequate bone marrow and organ function, and no history of active cardiac dysfunction were randomized 1:1 to receive either ribociclib (600 mg/d, 3 weeks on/1 week off) + letrozole (2.5 mg/d, continuous) or placebo + letrozole. The primary end point was locally assessed PFS. The data cutoff for this analysis was January 29, 2016. Results: Baseline demographics, patient disposition, and prior therapy were well balanced across treatment groups in the US subset (N=213; ribociclib group, n=100; placebo group, n=113). Median treatment duration was 16.3 months. In US patients, median PFS was significantly prolonged in the ribociclib group (median PFS, not reached [NR]; 95% CI, 17.1 months to NR) versus the placebo group (median PFS, 14.4 months [95% CI, 11.1–18.4 months]; hazard ratio, 0.451 [95% CI, 0.281–0.724]; P=0.000363), with a median follow-up of 11.0 months. In a subsequent preplanned analysis of overall survival, median PFS was 27.6 months in the ribociclib group versus 15.0 months in the placebo group (hazard ratio, 0.527; 95% CI, 0.351–0.793). The overall response rate (ORR) was significantly greater in the ribociclib group (ORR, 38.0%; 95% CI, 28.5–47.5%) versus the placebo group (ORR, 26.5%; 95% CI, 18.4–34.7%; P=0.040). A trend toward benefit was observed with ribociclib in all subgroups (including age, disease burden, prior therapy, and biomarker status), which was consistent with the overall population. No on-treatment deaths occurred. The most common all-grade adverse events, irrespective of causality, were neutropenia (ribociclib, 69.0%; placebo, 3.7%), nausea (ribociclib, 65.0%; placebo, 39.4%), fatigue (ribociclib, 56.0%; placebo, 46.8%), and diarrhea (ribociclib, 41.0%; placebo, 32.1%). The most common grade 3 (≥25% in either group) and grade 4 (≥10% in either group) AE was neutropenia (grade 3: ribociclib, 39.0%; placebo, 0%; grade 4: ribociclib, 14.0%; placebo, 0%). Two patients (2.0%) in the ribociclib group and none in the placebo group experienced febrile neutropenia. Conclusions: The US patients in the MONALEESA-2 study derived significant PFS benefit from ribociclib + letrozole compared with placebo + letrozole, with a 55% reduction in the relative risk of disease progression. The safety profile was consistent with and comparable to the global study population. Citation Format: Yardley DA, Hart L, Favret A, Blau S, Diab S, Richards D, Sparano J, Beck JT, Richards P, Ward P, Ramaswamy B, Tsai M, Pluard T, Tolaney S, Esteva F, Small T, Purkayastha D, Miller M, Hortobagyi G. Efficacy and safety of ribociclib plus letrozole in US patients enrolled in the MONALEESA-2 study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-27.

Abstract P5-21-18: Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study

Abstract Background: In the Phase III MONALEESA-2 study (NCT01958021), ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). The optimal treatment sequence following first-line CDK4/6i-based therapy is not yet known. Here we report the subsequent therapies received following discontinuation from MONALEESA-2. Methods: The MONALEESA-2 study enrolled 668 patients (pts) with HR+, HER2– ABC. Pts were randomized 1:1 to receive RIB (600 mg/day; 3-weeks-on/1-week-off) + LET (2.5 mg/day; continuous) or PBO + LET. Following discontinuation of MONALEESA-2 study treatment, pts were followed for information regarding post-study treatment, including type and duration of therapy. Results: At data cut-off (January 2, 2017), the median duration of follow-up was 26.4 months. Median PFS was 25.3 vs 16.0 months in the RIB + LET vs PBO + LET arms (hazard ratio=0.568; 95% confidence interval [CI]: 0.457–0.704; p=9.63x10–8). 203 (60.8%) vs 246 (73.7%) pts had discontinued RIB + LET vs PBO + LET. The median time to end of treatment was 20.3 months in the RIB + LET arm vs 13.7 months in the PBO + LET arm. First subsequent antineoplastic treatment was reported for 172/203 (84.7%) vs 212/246 (86.2%) pts who received RIB + LET vs PBO + LET; second subsequent therapy was reported for 45/203 (22.2%) vs 68/246 (27.6%) pts. The median time to first subsequent therapy (from randomization to the first post-study dose of therapy) was 24.2 (95% CI: 20.9–27.6) vs 16.7 (95% CI: 14.8–19.3) months in pts who received RIB + LET vs PBO + LET; median time to initiation of second subsequent therapy was not reached in either arm. The most common type of first subsequent therapy was single-agent hormonal therapy in 90 (44.3%) vs 87 (35.4%) pts who discontinued RIB + LET vs PBO + LET; chemotherapy was the most common second subsequent therapy in 20 (9.9%) vs 36 (14.6%) pts. Chemotherapy alone was the first subsequent treatment after MONALEESA-2 discontinuation in 32 (15.8%) vs 55 (22.4%) pts treated with RIB + LET vs PBO + LET. Conclusions: RIB + LET significantly prolongs PFS and delays the start of subsequent lines of therapy vs PBO + LET in pts with HR+, HER2– ABC. The most common first subsequent therapy following discontinuation of RIB + LET or PBO + LET was single-agent hormonal therapy, and fewer pts treated with RIB + LET received subsequent chemotherapy compared with those who received PBO + LET. Citation Format: Blackwell KL, Paluch-Shimon S, Campone M, Conte P, Petrakova K, Favret A, Blau S, Beck JT, Miller M, Sutradhar S, Monaco M, Burris HA. Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-18.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients

Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.