Distant Relapse-free Survival Rates Research Articles

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-year treatment period in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-year efficacy results from a prespecified overall survival (OS) interim analysis. In the intent-to-treat population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with hazard ratios of 0.680 (95% CI, 0.599 to 0.772) for IDFS and 0.675 (95% CI, 0.588 to 0.774) for DRFS. This persistence of abemaciclib benefit translated to continuous separation of the curves with a deepening in 5-year absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with rates of 6% and 5.3% at 4 years and 4.8% and 4.1% at 3 years. With fewer deaths in the abemaciclib plus ET arm compared with the ET-alone arm (208 v 234), statistical significance was not reached for OS. No new safety signals were observed. In conclusion, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence beyond the completion of treatment. The increasing absolute improvement at 5 years is consistent with a carryover effect and further supports the use of abemaciclib in patients with high-risk EBC.

Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study.

Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial. To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE. Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs). Overall, 501 Chinese patients were included (abemaciclib + ET, n = 259; ET, n = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea. At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients. ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).

Optimal timing of re-excision in synovial sarcoma patients: Immediate intervention versus waiting for local recurrence.

To investigate the difference in efficacy of re-excision in synovial sarcoma patients with and without residual tumor following unplanned excision, and to compare the prognostic outcomes of immediate re-excision versus waiting for local recurrence. This study included synovial sarcoma patients who underwent re-excision at our center between 2009 and 2019, categorized into groups based on unplanned excision and local recurrence. Analyzed endpoints included overall survival (OS), local recurrence-free survival (LRFS), and distant relapse-free survival (DRFS). Prognostic factors associated with these three different survival outcomes were analyzed through the use of Kaplan-Meier curves and Cox regression approaches. In total, this study incorporated 109 synovial sarcoma patients, including 32 (29.4%) with no residual tumor tissue identified after re-excision, 31 (28.4%) with residual tumor tissue after re-excision, and 46 (42.2%) with local recurrence after initial excision. Patients were assessed over a median 52-month follow-up period. The respective 5-year OS, 5-year LRFS, and 5-year DRFS rates were 82.4%, 76.7%, and 74.2% for the nonresidual group, 80.6%, 80.4%, and 77.3% for the residual tumor tissue group, and 63.5%, 50.7%, and 46.3% for the local recurrence group. There was no significant difference in OS of nonresidual group and residual group patients after re-excision (p = 0.471). Concurrent or sequential treatment with chemotherapy and radiotherapy significantly reduced the risk of metastasis and mortality when compared with noncombined chemoradiotherapy, and was more effective in the local recurrence group (p < 0.05). Prompt and adequate re-excision is crucial for patients with synovial sarcoma who undergo initial inadequate tumor excision, and their prognosis is significantly better compared with patients who delay re-excision until local recurrence.

107P Results in Chinese patients from pre-planned overall survival interim analysis in monarchE: Abemaciclib plus adjuvant endocrine therapy for high risk HR+, HER2- early breast cancer

Abemaciclib (oral CDK4 and 6 inhibitor) plus endocrine therapy (ET) as adjuvant treatment demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in Chinese patients (pts) with Hormone Receptor (HR+)-positive and human epidermal growth factor 2 (HER2)-negative high risk early breast cancer (EBC). This combination therapy provided sustained clinical benefits at the pre-planned overall survival interim analysis (OS IA2). Here we present the results of the subset of Chinese patients from monarchE at OS IA2. The overall study design was previously reported. Pts were randomized 1:1 to receive Abemaciclib + ET or ET alone. Eligible pts with ≥4 positive nodes, or 1-3 nodes and Grade 3 disease and/or tumor size ≥5 cm were included in Cohort 1 (C1); pts with 1-3 nodes and central Ki-67 ≥20% who did not meet entry criteria for C1 were included in Cohort 2 (C2). Analyses were conducted in Chinese pts enrolled from Mainland China, Hong Kong, and Taiwan in the intent-to-treat (ITT) population (501 pts), consisting of C1 (440 pts) and C2 (61 pts). At the time of data cutoff (July 1, 2022), all Chinese pts were off treatment with median follow-up of around 41 months. Sustained benefits of IDFS (HR=0.563, 95%CI: 0.343-0.923) and DRFS (HR=0.586, 95%CI: 0.341-1.006) were observed in Chinese pts in the ITT, with clinically meaningful improvement in the 4-year IDFS rates (88.5% vs 79.6%) and DRFS rates (90.0% vs 82.4%). In C1, the HR for IDFS was 0.582 (95%CI: 0.351-0.965) and DRFS was 0.610 (95%CI: 0.350-1.063), and a consistent benefit of abemaciclib was observed regardless of Ki-67 index. There were limited events of deaths in Chinese pts (abemaciclib plus ET vs ET: 6 [2.3%] vs 5 [2.1%]). No new safety signals were observed in Chinese pts. Consistent with reported results for the overall ITT population, abemaciclib combined with ET demonstrated clinically meaningful and sustained IDFS and DRFS benefits among Chinese pts with HR+, HER2-, high risk EBC and continued separation of the IDFS and DRFS curves. The OS data remain immature and follow-up is ongoing.

New Scale Predicting Distant Recurrence in Locally Advanced Lower Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (nCRT) for locally advanced lower rectal cancer (LALRC) is effective in preventing locoregional recurrence; however, it is less effective for preventing distant recurrence. This study aimed to evaluate a new scale for predicting distant recurrence before administering nCRT. Sixty-three patients underwent nCRT for LALRC between 2009 and 2016 at the Tokyo Women's Medical University. Of these, 51 consecutive patients who underwent curative surgery were enrolled in this study. Patients with ≥cT3 status or cN-positive LALRC were classified into three groups before nCRT based on the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR): high-risk, NLR ≥3.2 and LMR <5.0; intermediate-risk, NLR <3.2 and LMR ≥5.0 or NLR ≥3.2 and LMR <5.0; and low-risk, NLR <3.2 and LMR ≥5.0. Independent risk factors associated with distant relapse-free survival were analysed using the Cox proportional hazards model. Relapse-free survival from distant metastasis was evaluated using the log-rank test. Patient characteristics and tumour-associated factors were not significantly different between the groups. Distant recurrence in the high-, intermediate-, and low-risk groups was 61.5%, 42.9%, and 20.8% (p=0.046), respectively. In the multivariate analysis, the new scale was an independent risk factor for distant relapse-free survival (high-risk vs. low-risk groups, p=0.004 and intermediate-risk vs. low-risk groups, p=0.055). The 3-year distant relapse-free survival rate in the high-, intermediate-, and low-risk groups was 38.5%, 56.3%, and 81.7% (p=0.028), respectively. A new scale combining the pre-nCRT NLR and LMR was independently associated with distant relapse-free survival. The new scale for LALRC may aid selection for total neoadjuvant chemotherapy.

Abstract GS1-09: Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: results from a pre-planned monarchE overall survival interim analysis, including 4-year efficacy outcomes

Abstract Background Adjuvant abemaciclib (a CDK4 and 6 inhibitor) combined with ET resulted in significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high risk EBC in the monarchE trial, and is an approved adjuvant therapy for these patients. Here we present efficacy results from a pre-specified overall survival interim analysis (OS IA2) which was planned to occur 2 years (yrs) after the primary outcome analysis. Methods Pts were randomized (1:1) to receive ET for up to 10 yrs +/- abemaciclib for 2 yrs (study treatment period). High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN), or 1-3 ALN with either Grade 3 disease and/or tumor ≥5 cm (Cohort 1). While the proliferation biomarker Ki-67 was centrally assessed in all pts with available tissue sample, an additional smaller group of pts with 1-3+ ALN and central Ki-67 ≥20% as the only high-risk feature were included (Cohort 2). The intent-to-treat (ITT) population consisted of both Cohort 1 (5120 pts) and Cohort 2 (517 pts). Hazard ratios (HR) were estimated using Cox proportional hazard model. Results At a median follow-up of 42 months, all pts were off abemaciclib. IDFS and DRFS data illustrate a sustained benefit beyond the treatment period. In the ITT population, the HR for IDFS was 0.664 (95% CI: 0.578, 0.762) and DRFS was 0.659 (95% CI: 0.567, 0.767). At 4 yrs, this reflected an improvement in IDFS rates from 79.4% to 85.8% (absolute difference 6.4%), and in DRFS rates from 82.5% to 88.4% (absolute difference 5.9%). The continued separation of the curves was associated with an increase in absolute benefit in IDFS 4-year rates compared to 2-and 3-year IDFS rates (absolute difference 2.8% and 4.8% respectively). While OS remained immature, there was a lower number of deaths observed in the abemaciclib plus ET arm compared to the ET alone arm (157 [5.6%] vs 173 [6.1%], HR 0.929 [95% CI: 0.748, 1.153], p = 0.503), suggesting that the robust benefit in IDFS and DRFS began to translate into a numerically favorable OS HR. As previously described, within Cohort 1, a Ki-67 index of ≥20% was associated with a worse prognosis, but similar abemaciclib treatment effects were observed regardless of Ki-67 index. No new safety signals were observed. Conclusion The clinically meaningful benefit of adjuvant abemaciclib added to ET in HR+, HER2-, node-positive, high-risk EBC persists beyond completion of abemaciclib therapy, yielding an increase in absolute IDFS and DRFS benefit at 4 yrs. While OS remains immature at this time, the lower number of deaths in the abemaciclib arm compared to the ET arm suggest that a survival signal favoring abemaciclib is emerging. Citation Format: Stephen Johnston, Masakazu Toi, Joyce O’Shaughnessy, Priya Rastogi, Mario Campone, Patrick Neven, Chiun Sheng Huang, Jens Huober, Georgina Garnica Jaliffe, Irfan Cicin, Sara Tolaney, Matthew P. Goetz, Hope Rugo, Elżbieta Senkus, Laura Testa, Lucia Del Mastro, Chikako Shimizu, Ran Wei, Ashwin Shahir, Maria Munoz, Belen San Antonio, Valerie Andre, Nadia Harbeck, Miguel Martín. Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: results from a pre-planned monarchE overall survival interim analysis, including 4-year efficacy outcomes [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 GS1-09.

Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2-, node-positive, high-risk early breast cancer.

Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2- tumors may have different tumor biology and treatment response compared to postmenopausal patients. We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2- EBC in monarchE. Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated. Patients were stratified by menopausal status (premenopausal versus postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician's choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months). Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population. Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.

Association between tumor 18F-fluorodeoxyglucose metabolism and survival in women with estrogen receptor-positive, HER2-negative breast cancer

We examined whether 18F-fluorodeoxyglucose metabolism is associated with distant relapse-free survival (DRFS) and overall survival (OS) in women with estrogen receptor (ER)-positive, HER2-negative breast cancer. This was a cohort study examining the risk factors for survival that had occurred at the start of the study. A cohort from Asan Medical Center, Korea, recruited between November 2007 and December 2014, was included. Patients received anthracycline-based neoadjuvant chemotherapy. The maximum standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was measured. The analysis included 466 women. The median (interquartile range) follow-up period without distant metastasis or death was 6.2 (5.3–7.6) years. Multivariable analysis of hazard ratio (95% confidence interval [CI]) showed that the middle and high tertiles of SUV were prognostic for DRFS (2.93, 95% CI 1.62–5.30; P < 0.001) and OS (4.87, 95% CI 1.94–12.26; P < 0.001). The 8-year DRFS rates were 90.7% (95% CI 85.5–96.1%) for those in the low tertile of maximum SUV vs. 73.7% (95% CI 68.0–79.8%) for those in the middle and high tertiles of maximum SUV. 18F-fluorodeoxyglucose PET/CT may assess the risk of distant metastasis and death in ER-positive, HER2-negative patients.

Clinical Significance and Risk Factors of Local Recurrence in Synovial Sarcoma: A Retrospective Analysis of 171 Cases.

Objective: To investigate risk factors of local recurrence of synovial sarcoma and the impact of local recurrence on survival.Methods: We retrospectively reviewed clinical data of patients with II to IIIB (AJCC8) synovial sarcoma who underwent surgery at our center between March 2005 and December 2016. Data relating clinicopathological factors, treatment and prognosis were collected. The impact of local recurrence on overall survival (OS), local recurrence-free survival (LRFS), and distant relapse-free survival (DRFS) were analyzed. The prognostic factors associated with local recurrence were also analyzed using Kaplan-Meier Curves and Cox regression analysis.Results: A total of 171 patients were included in this analysis. After a median follow-up of 48 months, 66 patients (38.6%) experienced local recurrence. The 5-year OS, LRFS, and DRFS rates of patients with local recurrence were 37.6, 6.1, and 24.1%, respectively. Multivariate analysis showed that larger initial tumors, multiple recurrences, positive resection margins, marginal resection, and lack of adjuvant therapy were associated with higher local recurrence.Conclusion: Local recurrence of synovial sarcoma is associated with distant metastasis and poor survival. Chemoradiation improves the prognosis of patients with local recurrence, in particular those for which recurrence occurs shortly after initial treatment.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study

Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. At the primary outcome analysis, with 19 months median follow-up time, abemaciclib+ ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR)= 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P= 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR= 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR= 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. Abemaciclib+ ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

VP8-2021: Adjuvant abemaciclib combined with endocrine therapy (ET): Updated results from monarchE

Adjuvant abemaciclib (CDK4 & 6 inhibitor) combined with ET provides significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high risk early breast cancer (EBC). Updated results with a median follow-up of 27 months are presented. Pts were randomized (1:1) to receive ET for up to 10 years (yrs) +/- abemaciclib for 2 yrs. Pts had ≥4+ axillary lymph nodes (ALN), or 1-3+ ALN and either grade 3 disease or tumor ≥5 cm (Cohort 1), or 1-3+ ALN and centrally tested Ki-67 ≥20% (Cohort 2). For the ITT (cohort 1+2) and Ki-67 populations, hazard ratio (HR) was estimated using Cox proportional hazard model (data cutoff 1 April 2021). Exploratory analyses estimated the piecewise HR within each yr in the ITT. With 90% of pts having completed or discontinued the 2-yr study treatment period, the magnitude of IDFS benefit deepened (HR=0.696, 95% CI=0.588, 0.823; nominal p<0.0001) and DRFS benefit was maintained (HR=0.687, 95% CI=0.571, 0.826; nominal p<0.0001). At 3 yrs, absolute improvement in IDFS and DRFS rates were 5.4% and 4.2%, respectively. Abemaciclib benefit deepened during the treatment period (estimated IDFS/DRFS piecewise HRs at yr 0-1 0.795/0.732, yr 1-2 0.681/0.675) and persisted after the 2-yr treatment period (2+ yr IDFS/DRFS piecewise HRs 0.596/0.692). Estimated IDFS rates in the control arm of Cohort 1 (Ki-67 High vs Low) confirmed the prognostic value of Ki-67; however, abemaciclib benefit was consistent regardless of Ki-67 index (table). Overall, AE profile was similar to the prior analysis.Table: VP8-2021IDFSDRFSAbemaciclib + ETETHR (95% CI)Abemaciclib + ETETHR (95% CI)ITT (Cohort 1+2), N = 5637 Patients, N280828290.696 (0.588, 0.823)280828290.687 (0.571, 0.826) Events, n232333191278 3-Year Rates88.8%83.4%90.3%86.1%Ki-67 High (Cohort 1+2), N = 2498 Patients, N126212360.663 (0.524, 0.839)126212360.639 (0.494, 0.827) Events, n11817297146 3-Year Rates86.8%80.8%88.3%84.3%Cohort 1-Ki-67 High, N = 2003 Patients, N10179860.626 (0.488, 0.803)10179860.599 (0.456, 0.787) Events, n10415885135 3-Year Rates86.1%79.0%87.8%82.6%Cohort 1-Ki-67 Low, N = 1914 Patients, N9469680.704 (0.506, 0.979)9469680.679 (0.473, 0.975) Events, n62865073 3-Year Rates91.7%87.2%93.1%89.1% Open table in a new tab The benefit of adjuvant abemaciclib added to ET is strengthened within and beyond the 2-yr treatment period for pts with HR+, HER2-, node-positive, high risk EBC. High Ki-67 was prognostic, but not predictive of abemaciclib benefit. Safety profile remains acceptable for pts with EBC treated with curative intent.

Efficacy of perioperative chemotherapy for synovial sarcoma: a retrospective analysis of a Nationwide database in Japan

BackgroundSynovial sarcoma is an aggressive but chemosensitive soft-tissue tumor. We retrospectively analyzed the efficacy of perioperative chemotherapy for synovial sarcoma with data from the nationwide database, Bone and Soft Tissue Tumor Registry in Japan.MethodsThis study included 316 patients diagnosed with synovial sarcoma between 2006 and 2012. Oncologic outcomes were analyzed using a Cox-hazard regression model. Moreover, the effects of perioperative chemotherapy on outcomes were evaluated using a matched-pair analysis. The oncologic outcomes of patients who did or did not receive chemotherapy were compared (cx + and cx-).ResultsMultivariate analysis revealed significant correlations of age (over 40, hazard ratio [HR] = 0.61, p = 0.043), margin status (marginal resection, HR = 0.18, p < 0.001 and intralesional resection, HR = 0.30, p = 0.013 versus wide resection) with overall survival; surgical margin type (marginal resection, HR = 0.14, p = 0.001 and intralesional resection, HR = 0.09, p = 0.035 versus wide resection) with local recurrence; and postoperative local recurrence (HR = 0.30, p = 0.027) and surgical margin (marginal resection, HR = 0.31, p = 0.023 versus wide resection) with distant relapse-free survival.Before propensity score matching, perioperative chemotherapy was mainly administered for young patients and patients with deeper tumor locations, larger tumors, more advanced-stage disease, and trunk location. The 3-year overall survival, local control, and distant relapse-free survival rates were 79.8%/89.3% (HR = 0.64, p = 0.114), 89.6%/93.0% (HR = 0.37, p = 0.171) and 71.4%/84.5% (HR = 0.60, p = 0.089) in the cx+/cx- groups, respectively. After propensity score matching, 152 patients were selected such that the patient demographics were nearly identical in both groups. The 3-year overall survival, local control, and distant relapse-free survival rates were 71.5%/86.0% (HR = 0.48, p = 0.055), 92.5%/93.3% (HR = 0.51, p = 0.436) and 68.4%/83.9% (HR = 0.47, p = 0.046) in the cx+/cx- groups, respectively.ConclusionThis large-sample study indicated that the margin status and postoperative disease control were associated directly or indirectly with improved oncologic outcomes. However, the efficacy of perioperative chemotherapy for survival outcomes in synovial sarcoma patients was not proven in this Japanese database analysis.

Efficacy and safety analysis of Chinese patients in monarchE: Abemaciclib combined with adjuvant endocrine therapy for high risk HR+, HER2- early breast cancer.

522 Background: In monarchE, abemaciclib (oral CDK4&amp;6 inhibitor) plus endocrine therapy (ET) as adjuvant treatment for HR+, HER2- high risk early breast cancer (EBC), demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) compared to ET alone. Here we present the efficacy and safety analysis of Chinese patients from monarchE. Methods: The overall study design was reported previously. Eligible patients were randomized to receive abemaciclib (150 mg BID for 2 years) combined with standard adjuvant ET or ET alone. The primary endpoint was IDFS per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety. Exploratory subgroup analyses were conducted among Chinese patients enrolled from Mainland China, Hong Kong, and Taiwan in the intent-to-treat (ITT) population. Results: A total of 501 Chinese patients were randomized to receive abemaciclib plus ET (259 patients) or ET alone (242 patients). At the time of data cutoff (July 8, 2020), 356 (71.1%) patients were still in the 2-year treatment period. A total of 26 IDFS events were observed (11 and 15 events in abemaciclib plus ET and ET arm, respectively). Comparing to ET alone, abemaciclib combined with ET reduced the risk of developing invasive disease or death by 34.3% (HR: 0.657, 95% CI: 0.301, 1.435) for Chinese patients, together with a clinically meaningful improvement in the 2-year IDFS rate (95.6% vs 92.1%). The addition of abemaciclib to ET also resulted in an improvement in DRFS (HR: 0.601, 95% CI: 0.245, 1.477) for Chinese patients, with the 2-year DRFS rate at 96.7% (ET alone: 93.4%). In the abemaciclib arm, the most frequent treatment-emergent adverse events (TEAEs) and grade ≥3 TEAEs: diarrhea (90.3% and 5.0%), leukopenia (76.8% and 21.2%), and neutropenia (76.4% and 23.9%), respectively. Conclusions: Abemaciclib combined with adjuvant ET demonstrated clinically meaningful IDFS and DRFS benefits among Chinese patients with HR+, HER2-, high risk EBC, which was consistent with the ITT population as reported previously. The safety profile of abemaciclib in Chinese EBC patients was consistent with global population and also with that observed in Chinese metastatic breast cancer patients. Clinical trial information: NCT03155997.

Recurrence risk in early breast cancer as defined by clinicopathologic features.

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p &lt; .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p &lt; .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p &lt; .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p &lt; .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p &lt; .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

Abemaciclib combined with adjuvant endocrine therapy in patients with high risk early breast cancer who received neoadjuvant chemotherapy (NAC).

517 Background: monarchE, a phase 3, open-label, randomized study evaluating abemaciclib combined with adjuvant endocrine therapy (ET) compared to ET alone in patients with HR+, HER2-, high risk early breast cancer (EBC), resulted in a statistically significant improvement in invasive disease-free survival (IDFS) (HR = 0.713; 95% CI: 0.583, 0.871). NAC is used in patients with HR+, HER2- EBC at higher risk of recurrence despite often limited response, suggesting a need for enhanced adjuvant ET. Methods: Patients with ≥4 positive notes (LNS), or 1-3 LNS and either Grade 3 disease, tumor size ≥5 cm, or central Ki-67 ≥20% were eligible. Prior chemotherapy (NAC, adjuvant, none) was one of the stratifications factors. Prior therapy and tumor characteristics prior to study entry were collected. Here, we present the results of the prespecified subgroup of patients who received NAC. Results: Out of 5,637 randomized patients, 2056 (36.5%) received NAC. For 84.8%, the chosen regimen included anthracycline + cyclophosphamide + taxane, for 4.4%, it included anthracycline + taxane. A total of 1044 (50.8%) patients who received NAC had a radiologic tumor size between 2-5 cm and 599 (29.1%) had tumors ≥5 cm at diagnosis. 6.2%, 49.4% and 36.7% of patients had tumors with histologic Grade 1, 2, 3 respectively. 55.2% of patients had LNS ≥4+ and 44.4% had 1-3+ LNS. Central Ki-67 prior to NAC was ≥20% in 64.8% of patients with available Ki-67 results (664 (32.3%) patients had missing Ki-67 results). Evaluation of clinical and pathological measures of response will be presented. A multivariate cox regression analysis of IDFS in the intent-to-treat (ITT) population, identified prior chemotherapy as prognostic, suggesting patients who received NAC were at risk of a worse outcome. Primary outcome efficacy data for patients who received NAC are shown in the table below. Abemaciclib + ET demonstrated treatment benefit in terms of IDFS vs ET alone (HR: 0.614 95% CI: 0.473, 0.797) with 2-year IDFS rates of 87.2% vs 80.6%, respectively. The addition of abemaciclib to ET resulted in an improvement in distant relapse-free survival (DRFS) (HR: 0.609, 95% CI: 0.459, 0.809), with 2-year DRFS rates of 89.5% and 82.8%, respectively. Safety profile was similar to the overall safety population. Conclusions: Patients with HR+, HER2- EBC who received NAC were noted to be at a higher risk of recurrence. In this subgroup, abemaciclib combined with ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS, which was numerically greater than in the ITT population. Safety data were consistent with abemaciclib safety profile. Clinical trial information: NCT03155997. [Table: see text]

Abstract PS1-01: Combined analysis of the WORTH 1 and WORTH 2 studies of ipsilateral breast tumor recurrence after breast conservative surgery without radiotherapyusing the “5-mm thick slice and 5-mm free margin method”

Abstract Background: Breast conserving surgery with radiotherapy is one of the standard treatment methods for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor positive breast cancer with breast conserving surgery and hormone therapy without radiotherapy. Two sequential prospective studies were conducted to examine the efficacy of breast conserving surgery without radiotherapy from 2002. Patients and Methods: Primary breast cancer patients were divided into the WORTH 1 (n=123) group (Oct. 2002 and Mar. 2005) and the WORTH 2 (n=198) group (Dec. 2006 and Nov. 2011) and the data was retrospectively combined and analyzed. The eligibility criteria of the two sequential studies were a tumor ≥3cm determined by palpation, pathologically node negative by axillary dissection or sentinel node biopsy and M0, no preoperative treatment, postmenopausal patients ≥50 years of age at surgery, no tumor cells within 5 mm from the margins, no lymphatic invasion around the primary tumor, and estrogen receptor positive. The surgical specimens were sliced at 5 mm intervals and all the slices were examined microscopically. Postoperative radiotherapy was not conducted and adjuvant chemotherapy was optional. The patients were treated with tamoxifen or anastrozole in WORTH 1 and anastrozole in WORTH 2 for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival and distant relapse-free survival (DRFS) were recorded as the interval from initial surgery until IRTR or distant relapse. The factors related to IBTR were evaluated using the proportional hazard model. Patients who did not develop IBTR or distant relapse were statistically censored at the time of the last follow-up or death. Survival rates were calculated using the Kaplan-Mayer method. Statistical analyses were conducted using the log rank test. Values &amp;lt; 0.05 were considered statistically significant. Results: The median age at surgery was 65 (range 50-84). The median tumor size was 1.5 cm (range 0-4.0 cm). The median follow-up period for IBTR was 95 months (range 4-192 months). Only 3 patients were treated with adjuvant chemotherapy. The 5- and 10-year overall survival rates were 98.7% and 95.1%, respectively and the 5- and 10-year distant DRFS rates were 99.3% and 96.3%, respectively. The 5- and 10-year IBTR free rates were 97.0% and 89.7%, respectively. Older patients had significantly less IBTR rates (5-year IBTR free rates: 95.8% for ≤64 vs. 98.1% for ≥65, p=0.019). There was no difference in IBTR rates between the large and small tumors (5-year IBTR free rates: 96.9% ≤1.4 cm vs. 96.8% for ≥1.5 cm, p=0.094). PR positivity had a significantly lower IBTR free rates (5-year IBTR free rates: 98.3% for PR positive vs. 91.5% for PR negative, p=0.009). The age at surgery (≤64, p=0.017, Hazard ratio 3.07, 95% CI 1.22-7.70) and the PR status (PR negative, p=0.024, Hazard ratio 2.54, 95% Cl 1.13-5.69) independently affected the IBTR rates. Both the 5- and 10-year IBTR free rates of the patients who were ≥65 at surgery and had PR positive tumors (n=136) were 98.4%. Conclusions: The findings suggest that the “5-mm thick slice and 5-mm free margin” method may be effective in selecting patients who can be treated with breast conserving surgery and hormone therapy without radiotherapy. Citation Format: Norikazu Masuda, Shozo Ohsumi, Reiki Nishimura, Sadako Akashi-Tanaka, Kimito Suemasu, Hideko Yamauchi, Eriko Tokunaga, Tadashi Ikeda, Tsunehiro Nishi, Hiroto Hayashi, Yuichi Iino, Yuichi Takatsuka, Hideo Inaji. Combined analysis of the WORTH 1 and WORTH 2 studies of ipsilateral breast tumor recurrence after breast conservative surgery without radiotherapyusing the “5-mm thick slice and 5-mm free margin method” [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 PS1-01.

Outcome of surgical treatment of children and adolescents with primary malignant sacral tumours.

Little is known about the clinical outcome of children and adolescent patients with primary malignant sacral tumours. We retrospectively reviewed 40 patients with malignant sacral tumours aged ≤ 18years, receiving surgery based on the previous proposed surgical resection classification at our centre from 2003 to 2018. The following data were collected in the present study: age, gender, radiological images, detailed information ofthe surgical procedure, pulmonary and other metastasis at presentation, complications, local recurrence, metastasis, and death during the follow-up were recorded from the clinical and follow-up files. The mean follow-up was 30.7months (range, 5.2-146.7months). The incidence of local recurrence was 27.5% (11/40). Seven cases had surgical site infection andthere were 12cases of wound dehiscence. One had a deep venous thrombosis and one had femoral artery thrombosis. Three had fixation breakage and then received a revision. Tenty-two patients (22/40, 55%) were free of disease. A total of 13 deaths (13/40, 32.5%) were observed and the mean overall survival period was 17.1months (range, 6.3-34.2months), and a pulmonary metastasis occurred in 18 patients (45%, 18/45) at the 12.0 ± 10.3months (range, 2.2-35.3months) after initial surgery. The overall survival rates at one, two and five years were respectively 88.3%, 62.5%, and 51.9%. In the stratification analysis of young patients with primary malignant tumours at the sacrum after surgery, it revealed the influence of pathological grade, location, and age on the oncological outcomes. Kaplan-Meier estimateda survivorship curve of patients with high and low-grade malignant tumoursand showed statistical differences in the overall survival and distant relapse-free survival rates between two groups. Afterwards, the result demonstrated that paediatric patients aged ≤ 14years had worse prognosis than those aged > 14years. It is satisfactory for the outcome of surgical treatment of children and adolescent patients with primary malignant sacral tumours based on proposed surgical classification. Furthermore, paediatric patients aged ≤ 14years have the tendency of poor prognosis compared to adolescent aged > 14years.

Characteristics and clinical outcome of pT1a-b node-negative breast cancer.

OBJECTIVE:Tumor size, along with other clinicopathological characteristics, has a prognostic role in breast cancer. Recurrence risk tends to rise as tumor size increases. Early T-stage portends a good prognosis. We aimed to investigate the recurrence-free interval rates of T1abN0 group of early breast cancer.METHODS:Patients diagnosed with pT1a and T1b, lymph node metastasis-negative breast cancer were included in the study. Clinicopathologic characteristics including recurrence, distant metastasis, and final status of the patients were obtained retrospectively from the patient files.RESULTS:A total of 84 patients included. Twenty-six patients (31%) had T1a and 58 patients (69%) had T1b tumors. The 5-year distant relapse-free survival (DRFS) rate of T1ab tumors was 95.2%. The DRFS rate of T1a tumors was 96.2%, while the rate of T1b tumors was 94.8% (p=0.555). The 5-year RFS rate of T1ab tumors was 90.5%. The RFS rate of T1a tumors was 84.6%, whereas the rate of T1b tumors was 93.1% (p=0.359). The 5-year DRFS rate of hormone receptor positive group was 97%, Her-2 positive group was 81.8%, and triple negative group was 100% (p=0.041). The 5-year RFS rate of the hormone receptor positive group was 97%, Her-2 positive group was 72.7%, and triple negative group was 57.1% (p=0.001).CONCLUSION:The results of the study provided that both T1a and T1b tumors have a good and similar prognosis.

Sacral chordoma: a clinical review of 101 cases with 30-year experience in a single institution

BACKGROUNDLocal recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors. High-quality studies comparing presentation and treatments for primary and first local recurrent sacral chordoma tumors are sparse. PURPOSETo determine: whether there is a difference in how primary and tumors at first recurrence present; the overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a primary tumor; overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a first local relapse; if there any differences in overall survival, local relapse-free survival, and distant relapse-free survival rates between patients presenting with a primary tumor and those with a first local relapse. STUDY DESIGNRetrospective case series. PATIENT SAMPLEOne hundred one sacral chordoma cases. OUTCOME MEASUREOverall survival, local relapse-free survival, and distant relapse-free survival rates. METHODSBetween 1978 and 2013, 131 patients with sacral chordoma were seen. Of them, 17 patients (13%) presented with a history of more than one local recurrence. One patient (1%) presented with multiple distant metastases. Ten patients (8%) had less than 36 months of follow-up and had no event (eg, death, local recurrence, or distant metastasis). A total of 102 patients met our inclusion criteria: patients with primary or first recurrent tumors, without metastatic disease, who underwent surgery and with at least 36 months of follow-up. One patient (1%) died intraoperatively; therefore, 101 patients were included in the present analysis. Cox proportional hazards regression analysis was performed for primary and local recurrent tumor separately and to compare primary and local recurrent tumors. RESULTSWe analyzed 73 primary and 28 first time recurrent sacral chordomas. Tumor size at presentation was different for primary and recurrent tumors (primary median size: 158 cm3, interquartile range [IQR]: 46–634; recurrent median size: 39 cm3, IQR: 14–175; p=.001). Overall survival at 5 and 10years for the primary tumors was 79% and 59%, respectively. Local relapse-free survival at 5years was 86%. For primary tumors, not receiving radiation was an independent predictor for worse local relapse-free survival (hazard ratio [HR]: 0.20; 95% confidence interval [CI]: 0.0043–0.90; p=.004) and increased tumor size was an independent predictor for both worse overall survival (HR: 1.68; 95% CI: 1.38–2.42; p=.004) and worse distant relapse-free survival (HR: 2.25; 95% CI: 1.47–3.44; p<.001). For recurrent tumors, the 5- and 10-year overall survival was 65% and 40%, respectively. Local relapse-free survival at 5years was 79% for recurrent tumors. On bivariate analysis, increased tumor size was a significant predictor for worse survival (LR median: 338 mL; IQR: 218–503 mL; no LR median: 26 mL; IQR: 9–71 mL). A trend was seen toward better distant relapse survival for tumors presenting as a primary tumor (HR: 0.51; 95% CI: 0.25–1.06; p=.072). CONCLUSIONUsing a combination of surgical resection and adjuvant radiotherapy allowed us to obtain a good overall survival, local relapse-free survival, and distant relapse-free survival in patients presenting with either a primary tumor or with a first time local recurrent tumor.