BRCA1/2 germline pathogenic variants confer markedly elevated lifetime risks for breast, ovarian, prostate, and pancreatic cancers. Preimplantation genetic testing for monogenic disorders (PGT-M) is an embryo-selection step performed within an in vitro fertilization (IVF) cycle that enables carriers to select embryos unaffected by the familial pathogenic variant, substantially reducing-though not eliminating-the risk of transmission. Despite regulatory approval by ESHRE since 2003 and accumulating evidence of clinical and cost-effectiveness, PGT-M remains systematically underutilized in Türkiye. This study aimed to simultaneously assess PGT-M knowledge and attitudes among physicians managing BRCA-positive individuals and among patients and carriers themselves, to quantify the knowledge-action gap, and to characterize PGT counseling practices. A cross-sectional dual-survey study was conducted including 206 physicians and 72 BRCA1/2-positive individuals. Descriptive statistics and subgroup comparisons were performed. Binary logistic regression identified factors associated with adequate physician knowledge. Only 33.0% of physicians reported adequate perceived knowledge, whereas 80.1% considered it medically appropriate and 71.8% would recommend it, demonstrating a marked knowledge-attitude paradox. Excluding genetics and gynecology specialists, adequate perceived knowledge dropped to 16.2%. Among patients, 69.4% had never received PGT information during counseling, and only 16.7% would consider PGT. Younger patients (< 40 years) showed numerically higher receptivity (28.6% vs. 11.8% in those aged ≥ 40 years), although this difference was not statistically significant. In Turkish BRCA clinical practice, positive attitudes toward PGT coexist with substantial knowledge deficits. Patients under 40, who carry the greatest reproductive urgency and highest potential benefit from PGT, are more receptive but remain inadequately counseled. Integrating PGT into routine genetic counseling protocols, implementing specialty-targeted continuing medical education focusing on medical oncology and surgery, and establishing national oncofertility coordination may represent important strategies toward closing this gap.

Background: The phase 2 RIGHT Choice study showed a statistically significant median progression-free survival (mPFS) benefit with 1L RIB + ET vs combo CT (HR, 0.61; 95% CI: 0.43-0.87; P = .003) in pts with clinically aggressive HR+/HER2− ABC (Lu Y-S, et al. J Clin Oncol. Published online May 21, 2024). This exploratory analysis of the RIGHT Choice study examined efficacy of RIB + ET vs combo CT by intrinsic subtype and gene/signature expression levels. Methods: Pre/perimenopausal pts with no prior systemic therapy for aggressive HR+/HER2− ABC were randomized 1:1 to RIB + letrozole/anastrozole + goserelin or physician's choice of combo CT. Baseline tumor samples (n = 49) from pts enrolled in the trial were microdissected and underwent gene expression profiling by NanoString nCounter BC360 and PanCancer IO 360 panels. High and low baseline gene/signature expression levels were defined as greater and less than or equal to the median level, respectively. Results: Of the available samples from the RIB arm (n = 27), 6 (22.2%) were luminal A, 14 (51.9%) were luminal B, 6 (22.2%) were HER2E, and 1 (3.7%) was basal-like; in the CT arm (n = 22), 11 (50.0%) were luminal A, 9 (40.9%) were luminal B, and 2 (9.1%) were HER2E. The mPFS in the RIB vs CT arms was 32.5 mo vs not reached (NR) (HR, 0.88; 95% CI: 0.20-3.91) in luminal A, 38.0 vs 21.7 mo (HR, 0.64; 95% CI: 0.18-2.20) in luminal B, and 17.4 vs 8.0 mo (HR, 0.23; 95% CI: 0.03-1.66) in HER2E subtype. In the combined luminal B/HER2E set, which are known to be associated with poor prognosis, the mPFS was 38.0 vs 18.4 mo with RIB + ET vs combo CT (HR, 0.58; 95% CI: 0.21-1.62). In the RIB arm, pts with high ESR1 expression showed longer mPFS vs pts with low ESR1 expression (high vs low expression, mPFS, HR [95% CI]; 38.0 vs 32.5 mo, 0.52 [0.16-1.66]). Pts in the RIB arm with low expression of tumor inflammation or immune-related genes/cells, such as tumor inflammatory signature (TIS; BC360 panel) and T-cell (IO 360 panel) expression, had a longer mPFS than pts with high expression of these signatures (low vs high expression, mPFS, HR [95% CI]: TIS, NR vs 11.4 mo, 0.17 [0.04-0.76]; T cells, NR vs 10.3 mo, 0.2 [0.05-0.76]). In contrast to the results in the RIB arm, pts with low expression of immune-related genes/cells in the CT arm had a shorter mPFS than those with high expression of these genes (low vs high expression, mPFS, HR [95% CI]: TIS, 15.0 mo vs NR, 2.08 [0.62- 6.93]; T cells, 12.8 vs 18.4 mo, 1.8 [0.57-5.71]). For most other immune-related genes/cells expressions and signatures, a comparable consistent trend in PFS benefit for low vs high expression levels was observed, with a higher PFS benefit for low gene expression in the ribociclib arm, and a higher PFS benefit for high gene expression in the CT arm. Conclusions: This exploratory analysis showed a trend towards PFS benefit with RIB + ET vs combo CT in pts with luminal B/HER2E intrinsic subtypes, which are associated with poor prognosis. This analysis also suggest a more pronounced trend for PFS benefit with RIB + ET in pts with low baseline expression levels of immune-related genes. Contrary results in the CT arm suggest that these signatures warrant further studies on their potential predictive value. These data are hypothesis generating and should be interpreted with caution due to small sample sizes. Citation Format: Yen-Shen Lu, Chia-Lang Hsu, Eznal Izwadi Bin Mohd Mahidin, Sudeep Gupta, Erhan Gökmen, Elena Artamonova, Huang-Chun Lien, Hamdy Azim, Yoon-Sim Yap, Yesim Eralp, Seock-Ah Im, Fei Su, Yogesh Chattar, Estelle Roux, Melissa Gao, Nagi S. El Saghir. First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of RIGHT Choice by intrinsic subtype & gene & signature expression [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS2-06.

Breast cancer represents the most frequently diagnosed malignancy among women globally, with significant progress in systemic therapy, surgical techniques, and radiotherapy contributing to improved clinical outcomes. However, many clinical scenarios encountered in daily practice are not fully addressed by randomized trials, leaving persistent grey zones in the management of early-stage breast cancer. To meet these challenges, the multidisciplinary panel at Research Institute of Senology, Acıbadem University outlined experience-based recommendations for clinical situations typically faced in daily practice. Herein we aim to reflect both current evidence and institutional practice and provide practical guidance in areas where uncertainty persists. As breast cancer treatment continues to evolve, updates will be required to integrate emerging data and refine individualized patient care.

1069 Background: The phase II RIGHT Choice trial reported a statistically significant progression-free survival (PFS) benefit at the primary prespecified analysis and a 9-month (mo) benefit at the final analysis with 1L RIB + ET over combo CT in pts with clinically aggressive HR+/HER2– ABC. As liver mets in ABC indicate a worse prognosis, an analysis by liver mets status was performed (data cutoff: May 10 th , 2023). Methods: Pre- and perimenopausal women (N = 222) with no prior systemic therapy for clinically aggressive HR+/HER2− ABC were randomized 1:1 to receive RIB + letrozole or anastrozole + goserelin or physician's choice of combo CT. Enrolled pts had ABC for which combo CT was clinically indicated by physician’s judgment. Results: In total, 107 (RIB + ET, n = 54; combo CT, n = 53) and 115 (RIB + ET, n = 58; combo CT, n = 57) pts presented with or without liver mets, respectively. Pts with liver mets had PFS of 18.3 vs 12.7 mo and median time to treatment failure (mTTF) of 13.2 vs 8.3 mo with RIB + ET vs combo CT, respectively (Table). A clinical benefit rate (CBR) of 77.8% vs 67.9%, overall response rate (ORR) of 64.8% vs 60.4%, and median time to response (mTTR) of 6.4 vs 3.0 mo were seen in the RIB vs CT arm, respectively. Pts without liver mets had PFS of 25.2 vs 15.4 mo and mTTF of 24.0 vs 10.1 mo in the RIB vs CT arm, respectively, and similar CBR, ORR, and TTR regardless of treatment (tx). No new safety signals were observed in pts with liver mets. A numerically longer median time to deterioration (mTTD) in FACT-B total score was seen with RIB + ET vs combo CT in pts with and without liver mets. Conclusions: This analysis from RIGHT Choice showed similar clinically meaningful efficacy and quality-of-life benefits and no new safety signals for RIB + ET vs combo CT between pts with and without liver mets. These results support the 1L use of RIB + ET in pts with clinically aggressive HR+/HER2– ABC even in the presence of liver mets. Clinical trial information: NCT03839823 . Liver mets Tx arm n mPFS,mo(95% CI) HR(95% CI) mTTF,mo(95% CI) HR(95% CI) CBR a ,%(95% CI) ORR a ,%(95% CI) mTTR a ,mo(95% CI) HR(95% CI) mTTD (FACT-B total score) b ,mo HR(95% CI) Yes RIB + ET 54 18.3(10.3-24.0) 0.68(0.42-1.11) 13.2(10.2-21.2) 0.60(0.39-0.92) 77.8(64.4-88.0) 64.8(50.6-77.3) 6.4(4.6-23.9) 0.68(0.42-1.10) 37.7 0.68(0.34-1.34) Combo CT c 53 12.7(7.5-21.0) 8.3(5.3-12.8) 67.9(53.7-80.1) 60.4(46.0-73.5) 3.0(2.6-6.7) 18.4 No RIB + ET 58 25.2(18.6-NE) 0.57(0.34-0.93) 24.0(16.4-32.2) 0.44(0.29-0.69) 84.5(72.6-92.7) 67.2(53.7-79.0) 4.6(2.8-10.2) 0.81(0.52-1.28) NE 0.59(0.29-1.21) Combo CT c 57 15.4(8.8-20.0) 10.1(7.8-13.6) 80.7(68.1-90.0) 63.2(49.3-75.6) 4.5(1.4-8.2) 37.1 NE, not evaluable. a Without confirmation; b ≥7 point decrease; c docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine.

PURPOSE:A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). METHODS:In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS). RESULTS:Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. CONCLUSION:First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.

545 Background: In non-developed and developing countries, the 21 gene assay (Oncotype DX) test is expensive and not covered by private and social health insurance, which limits its use. However, clinicians need this test for treatment prediction in early stage breast cancer. Therefore, we aimed to predict the risk of recurrence in patients using artificial intelligence (AI) algorithms. Methods: This study was conducted with 437 early-stage breast cancer patients whose recurrence risk scores were determined by 21 Oncotype DX and were followed in 14 oncology centers in Turkey between 2012 and 2022. The optimum cut-off for the 21 gene assay risk score (RS) was found by ROC analysis using the patients' recurrence information (scale of RS ≥17: high risk, <17: low risk). In artificial intelligence prediction models, patients with a 21 gene assay risk score ≥17 were considered high risk. Additionally, algorithm predictions were made within other cut-offs recommended in the literature (<10, 11-25, >25). Python programming language was used in the analyses. The Random Forest (RF), Logistic regression (LG) and K-Nearest Neighbors (KNN) were used as AI prediction algorithms. Results: The study analyzed 437 women with an average age of 49.49±10.30. During the follow-up period from 2012 to 2022, 7.1% of the patients experienced a recurrence. AI prediction algorithms which were RF, LG, and KNN generated confusion matrices for two classes, with a threshold of 17 and 25. The algorithms were then applied to the dataset with risk score thresholds of 1-10, 11-25, and greater than 25, resulting in three classes. The dataset was analyzed using recall, precision, and F1 score values. The results showed that RF had the most accurate predictions for RS = 17 (Table). Conclusions: The use of artificial intelligence algorithms in predicting the risk of recurrence in early stage breast cancer is promising in determining treatment decisions for clinicians who cannot access genetic results. [Table: see text]

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common types of cancer with high mortality rates. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with a personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

1063 Background: The progression-free survival (PFS; primary endpoint) results from the Phase II RIGHT Choice trial demonstrated a statistically significant median PFS (mPFS) benefit of ≈1 y with RIB + ET over combo CT (mPFS, 24.0 vs 12.3 mo; hazard ratio [HR], 0.54; 95% CI, 0.36-0.79; P = .0007) in pts with aggressive HR+/HER2− ABC. Younger pts with aggressive ABC have a worse prognosis, which impacts treatment (tx) decisions. Hence, a subgroup analysis of key efficacy endpoints from RIGHT Choice by age (< 40 vs ≥ 40 y) was undertaken. Methods: Pre/perimenopausal pts (aged 18-59 y) with HR+/HER2− ABC and no prior systemic therapy for ABC were randomized 1:1 to either RIB with letrozole/anastrozole + goserelin or investigator’s choice of combo CT (docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine). Pts in the trial had ABC not amenable to curative therapy and for which combo CT was clinically indicated by physician’s judgment (ie, symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic non-visceral disease). Results: In total, 70 pts were aged < 40 y and 152 were aged ≥ 40 y. In the combo CT arm, pts aged < 40 y fared worse and had a shorter mPFS, shorter median time to tx failure (mTTF), and higher 3-month tx failure rate (TFR) than pts aged ≥ 40 y. Pts aged < 40 y showed a significant PFS benefit with RIB + ET vs combo CT (mPFS, not reached [NR] vs 10.2 mo; HR, 0.38). This PFS benefit with RIB + ET over combo CT was also observed in pts aged ≥ 40 y (21.2 vs 16.0 mo; HR, 0.71). Regardless of age, the mTTF was longer and the 3-month TFR was lower in the RIB + ET arm than the combo CT arm. The median time to response (mTTR), overall response rate (ORR), and clinical benefit rate (CBR) were similar between the two tx arms in both age groups. Conclusions: This analysis demonstrated a clinically meaningful PFS benefit and improved secondary outcomes with 1L RIB + ET over combo CT along with similar treatment responses in both tx arms in pts aged < 40 y as well as in those ≥ 40 y with aggressive HR+/HER2− ABC. This analysis supports RIB + ET as a preferred tx option in this pt population, including younger pts aged < 40 y. Clinical trial information: NCT03839823 . [Table: see text]

RIGHT Choice reported a statistically significant median progression-free survival (mPFS) benefit of ≈1 y with RIB + ET vs combo CT (24.0 vs 12.3 mo; HR, 0.54; P=.0007) in pre- or perimenopausal pts with HR+/HER2− ABC. We report outcomes in Asian and non-Asian pts from this trial. Pre- or perimenopausal pts with HR+/HER2− ABC and no prior systemic therapy for ABC were randomized to RIB + ET or investigator’s choice of combo CT (Table). Pts had ABC for which combo CT was clinically indicated by physician’s judgment (symptomatic visceral metastases, rapid disease progression/impending visceral compromise, or markedly symptomatic non-visceral disease). Pt characteristics between arms were balanced in the Asian (n=118) and non-Asian (n=104) subgroups. Similar characteristics were seen in Asian and non-Asian pts, with some differences in BMI (median, 23.7 vs 26.3 kg/m2) as well as the proportion with symptomatic non-visceral disease (7.6% vs 21.2%) and physician-assessed visceral crisis (69.5% vs 32.7%). The PFS benefit with RIB + ET vs CT was 15.0 mo (mPFS, 25.2 vs 10.2 mo; HR, 0.43) in Asian pts and 8.3 mo (21.1 vs 12.8 mo; HR, 0.75) in non-Asian pts. In both groups, the median time to treatment (tx) failure (mTTF) was longer and the 3-mo tx failure rate (TFR) was lower with RIB + ET vs CT. In Asian pts, the overall response rate (ORR) was higher with RIB + ET than CT, with similar clinical benefit rate (CBR) and median time to response (mTTR) in both arms. In non-Asian pts, the ORR and CBR were similar in both arms, with longer mTTR for RIB + ET vs CT. The safety profile in the subgroups was consistent with that of the overall pt population. This post hoc analysis confirmed a clinically meaningful PFS benefit with 1L RIB + ET vs combo CT in pre- or perimenopausal Asian and non-Asian pts with HR+/HER2− ABC.Table: 57MOSub- groupArmnmPFS (95% CI), moHR (95% CI)mTTF (95% CI), moHR (95% CI)3-mo TFR (95% CI), %ORR, %aCBR, %amTTR (95% CI), moaAsianRIB + ET6025.2 (17.1-NR)0.43 (0.25-0.74)19.5 (12.7-NR)0.42 (0.26-0.68)10.0 (3.8-20.5)71.781.74.6 (3.0-6.6)CTb5810.2 (8.3-18.4)8.5 (6.7-13.6)19.0 (9.9-31.4)56.974.14.7 (2.7-NR)Non-AsianRIB + ET5221.1 (10.2-NR)0.75 (0.42-1.32)18.6 (10.2-24.0)0.48 (0.29-0.80)13.5 (5.6-25.8)57.778.87.4 (4.4-NR)CTb5212.8 (8.8-18.4)8.8 (6.6-12.3)25.0 (14.0-38.9)63.571.22.9 (1.4-4.5)NR, not reached. a Unconfirmed; b Docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine. Open table in a new tab

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3–5

RIGHT Choice showed a statistically significant median progression-free survival (mPFS) benefit of ≈1 yr with first-line RIB + ET vs combo CT (HR, 0.54; P=.0007) in pts with aggressive HR+/HER2− ABC. As visceral crisis indicates need for a more rapidly efficacious treatment (tx), a subgroup analysis by visceral crisis status was performed. Pre/perimenopausal pts (N=222) with no prior systemic therapy for aggressive HR+/HER2− ABC were randomized 1:1 to RIB + letrozole/anastrozole + goserelin or physician's choice of combo CT. Visceral crisis assessment was based on physician's judgment, following ABC 3 guidelines available at the time. Overall, 116 (RIB + ET, n=61; CT, n=55) and 106 (RIB + ET, n=51; CT, n=55) pts presented with or without visceral crisis, respectively. In pts with visceral crisis, a mPFS of 12.9 mo was seen with RIB + ET vs 11.2 mo with combo CT (HR, 0.87). While in these pts the overall response rate (ORR) numerically favored RIB + ET, the time to treatment failure (TTF) and clinical benefit rate (CBR) were similar in both tx arms (Table). In pts with no visceral crisis, a mPFS benefit was seen with RIB + ET vs combo CT (24.0 vs 12.7 mo; HR, 0.34); also, TTF and CBR favored RIB + ET over combo CT. RIB + ET was associated with lower rates of symptomatic adverse events than combo CT in both groups. These interim results are based on the 12 Apr 2022 data cutoff; final results will be shown at ESMO 2023. This analysis shows similar PFS and TTF outcomes but greater ORR with RIB + ET vs combo CT in pts with physician-assessed visceral crisis. Clinically meaningful tx benefit with RIB + ET over combo CT was seen in pts with aggressive disease not classified as visceral crisis. These findings support RIB + ET over combo CT in pts with aggressive ABC even in the presence of visceral crisis.Table: 402PVisceral CrisisTx ArmnmPFS (95% CI), moHR (95% CI)mTTF, moHR (95% CI)ORR, %*CBR, %*YesRIB + ET6112.9 (9.9-25.2)0.87 (0.51-1.47)10.30.68 (0.43-1.08)72.177.0Combo CT†5511.2 (8.4-21.0)10.256.470.9NoRIB + ET5124.0 (21.1-NR‡)0.34 (0.18-0.63)24.00.29 (0.17-0.51)56.984.3Combo CT†5512.7 (8.3-17.5)8.563.674.5*Without image confirmation; †Docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine; ‡Not reached. Open table in a new tab

Background: Combination chemotherapy (CT) remains a standard of care in advanced breast cancer (ABC) with aggressive disease features (rapidly progressing or highly symptomatic disease, including life-threatening visceral crisis). To date, no data have been published on a head-to-head comparison of CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) vs combination CT in this patient (pt) population. RIGHT Choice, a randomized, open-label, multi-national, Phase II trial, investigated the efficacy and safety of first-line ribociclib (RIB) + ET vs combination CT in pre/perimenopausal pts with HR+/HER2− ABC with aggressive disease (where combination CT is clinically indicated by physician’s judgment). Here we report the results of the primary endpoint of progression-free survival (PFS) and key secondary endpoints from this study. Methods: Pre/perimenopausal pts with HR+/HER2− ABC (>10% estrogen receptor–positive [ER+]) and no prior systemic therapy for ABC were randomized 1:1 to receive either RIB (600 mg daily, 3 weeks on/1 week off) with letrozole/anastrozole + goserelin or investigator’s choice of CT (docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine). Randomization was stratified by presence of liver metastases and whether the disease-free interval (duration from date of complete tumor resection for primary breast cancer lesion to the date of documented disease recurrence) was less than two years. Pts included in the trial had ABC not amenable to curative therapy for which combination CT was clinically indicated by physician’s judgment (i.e., symptomatic visceral metastases, rapid progression of disease or impending visceral compromise, or markedly symptomatic non-visceral disease). Median PFS (mPFS) and median time to treatment failure (mTTF) were evaluated by Kaplan-Meier methods. Overall response rate (ORR) was also analyzed, with quality of life and biomarker analyses planned. RIGHT Choice is registered at ClinicalTrials.gov (NCT03839823). Results: A total of 222 pts (112 RIB + ET; 110 CT) were enrolled from Feb 2019 to Nov 2021. Pts with symptomatic visceral metastases (n=150; 67.6%), rapid disease progression (n=41; 18.5%), and markedly symptomatic non-visceral metastases (n=31; 14.0%) were included. Overall, 116 pts (52.3%) had visceral crisis based on guideline definitions. A majority of pts (n=190; 85.6%) had tumors that were ≥50% ER+. At data cutoff (Apr 12, 2022), median follow-up was 24.1 mo; 45.5% and 23.6% of pts remained on treatment in the RIB + ET arm and combination CT arm, respectively. The primary endpoint was met, with a statistically significant PFS benefit of ≈1 year for RIB + ET vs combination CT (mPFS, 24.0 vs 12.3 mo; hazard ratio, 0.54; 95% CI, 0.36-0.79; P=.0007). OS data were immature at data cutoff. The mTTF was ≈10 mo longer for RIB + ET vs CT (18.6 vs 8.5 mo; hazard ratio, 0.45; 95% CI, 0.32-0.63). The ORR was similar for RIB + ET vs CT (65.2% vs 60.0%). No new safety signals were observed in pts on RIB. Lower rates of treatment-related serious adverse events (AEs; 1.8% vs 8.0%) and lower rates of discontinuation due to treatment-related AEs (7.1% vs 23.0%) were seen with RIB + ET vs CT, respectively. AEs observed with combination CT were consistent with the published data. Conclusions: This analysis demonstrated a statistically significant and clinically meaningful PFS benefit with RIB + ET over combination CT in the first-line pre/perimenopausal pt population with aggressive HR+/HER2− ABC disease. This is the first study comparing a CDK4/6i + ET vs combination CT and demonstrating the superiority of RIB + ET in aggressive HR+/HER2− ABC. This evidence supports RIB+ ET use as a preferred option for this pt population. Citation Format: Yen-Shen Lu, Eznal Izwadi Bin Mohd Mahidin, Hamdy Azim, Yeşim ERALP, Yoon-Sim Yap, Seock-Ah Im, Julie Rihani, James Bowles, Teresa Delgar Alfaro, Jiwen Wu, Melissa Gao, Khemaies Slimane, Nagi El Saghir. Primary results from the randomized Phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2− advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy [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 GS1-10.