Quality-of-life and symptom severity in the PALLAS randomized trial of palbociclib with adjuvant endocrine therapy in early breast cancer (AFT-05, ABCSG-42, BIG-14-03, PrE0109)

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Background: Adjuvant ET is associated with improved survival in women with hormone receptor-positive early BC. Nonetheless, more than a quarter of women are non-adherent or discontinue therapy early. We aimed to identify whether baseline characteristics and changes in weight and patient-reported outcomes (PRO) early during the course of ET are associated with medication adherence behavior (MAB) in a prospective cohort. Methods: We enrolled women initiating or switching adjuvant ET for stage 0-III BC in a prospective clinic-based cohort. Participants completed PRO questionnaires at baseline, and 3, 6, and 12 months (mo) after initiating ET. PRO questionnaires included FACT-ES, the NIH PROMIS measures for pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance, and the MOS Sexual Functioning Scale. MAB was assessed by the Medication Adherence Questionnaire (MAQ). MAB was defined as high (MAQ score=0), or medium/low (MAQ score>0). Questionnaires were administered through the PatientViewpoint web-based interface. We tested changes in mean PRO scores from baseline to follow-up time points with paired t-tests. We explored associations between baseline characteristics, and changes in weight and PRO at 6 mo with MAB at 12 mo using Fisher's exact test, Wilcoxan rank sum tests and t-tests. P-values <0.05 were considered significant. Results: From March 2012 to December 2016, 336 women enrolled in the cohort. Mean age was 60 (range 26-90), 84% were Caucasian, and 67% were post-menopausal. Overall, 57% received an aromatase inhibitor, 43% received tamoxifen, and 28% received prior taxane chemotherapy. Median follow-up was 12 mo. At baseline, 61% were overweight/obese, and 21% gained >5% of baseline weight by 12 mo. Mean baseline and follow-up scores at 3, 6 and 12 mo were within 1 standard deviation of reference population means for all PRO measures. Compared to baseline, endocrine symptoms were increased at 3, 6 and 12 mo (p<0.05), while sexual function and depression did not differ between baseline and any follow-up time point (p>0.05). At 6 mo, anxiety was reduced, physical function was improved and pain impact was reduced compared to baseline (p<0.05). MAB was high for 71% of participants at 12 mo. Preliminary data demonstrate that, compared to those with high MAB at 12 mo, women with medium/low MAB at 12 mo took fewer concomitant medications at baseline, and had more improvement in anxiety and sexual function at 6 mo. MAB at 12 mo did not differ according to race, type of ET, baseline weight or PRO measures, or 6 mo change in weight or other PRO measures. Conclusions: Early changes in anxiety and sexual function during the course of adjuvant ET and the number of baseline concomitant medications may separate women with subsequent high versus medium/low MAB risk. Weight loss interventions and symptom management are needed for women receiving adjuvant ET during the first year of treatment. Our data will be used to create a model to predict MAB for validation studies and as the basis to devise interventions to improve adherence to adjuvant ET. Citation Format: Smith KL, Yeruva SLH, Blackford A, Huang C-Y, Westbrook KE, Harding BA, Smith A, Fetting J, Wolff AC, Jelovac D, Miller RS, Connolly R, Armstrong D, Nunes R, Visvanathan K, Stearns V. Predictors of adherence to adjuvant endocrine therapy (ET) for early breast cancer (BC) in a prospective clinic-based cohort [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 P3-12-02.

Patient-reported outcomes in the SERENA-6 trial of camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and emergent ESR1 mutations during first-line endocrine-based therapy.

Re: Combination of Adjuvant Hormonal and Radiation Therapy Significantly Prolongs Survival of Patients With pT2–4 pN+ Prostate Cancer: Results of a Matched Analysis

Patient-Centered Evaluation of Clinical Benefit in Acute Myeloid Leukemia: Importance of Early Engagement with Patients

Background: Most women with newly diagnosed breast cancer are of luminal type and will be offered 5-10 years of adjuvant endocrine therapy. Many women will not have a survival benefit from this therapy and 30% or more will struggle with side effects and quality of life issues. Breast Cancer Index (BCI) is a genomic biomarker for early-stage, ER+ breast cancer and has been validated to assess risk of late (5-10 yr) distant recurrence and predict likelihood of benefit from extended (>5y) endocrine therapy utilizing the HoxB13/IL17BR(H/I) ratio. H/I has also been shown to predict benefit from endocrine therapy in the early adjuvant setting. The objective of this study was to characterize the impact of BCI on endocrine therapy decision-making for early-stage breast cancer patients. Methods: Data was collected retrospectively from patients with early-stage luminal breast cancer treated at Breastlink who underwent BCI testing between 10/2014-5/2015. The impact of BCI test results were analyzed for 3 indications: 1) initiation of endocrine therapy for patients considering no adjuvant treatment; 2) patients 6 mo-4y post diagnosis struggling with side effects and desiring to discontinue endocrine therapy; and 3) patients beyond 4 years of adjuvant hormonal therapy deciding whether to extend therapy for an additional 5 years. Results: One hundred patients underwent BCI testing with median age 53 (range 35-77). The BCI assay was utilized in 14 cases at diagnosis, 54 cases at 6 mo-4y during therapy, and 32 cases at >4y post-diagnosis. In patients tested at time of diagnosis, 10/11 that were low risk for late recurrence and low likelihood of benefit from endocrine therapy chose not to initiate therapy, and 2/2 patients were high risk/high likelihood to benefit initiated therapy. One patient, a 72 year-old with low risk and high likelihood to benefit, declined therapy. In patients tested between 6 mo-4y on therapy, 30/30 patients were low risk and low likelihood of benefit chose to stop endocrine therapy, and 11/11 patients were high risk and high likelihood of benefit chose to continue. Of 7 patients that were low risk but high likelihood of benefit, 5 continued therapy. All 6 patients that were high risk but low likelihood of benefit chose to stop therapy. Of 32 patients tested after 4 years of adjuvant therapy, 13/13 were low risk and low likelihood of benefit chose to stop endocrine therapy at 5 years, and 8/8 were high risk and high likelihood of benefit chose to extend therapy to 10 years. All 5 patients that were high risk but low likelihood of benefit elected to stop, and 3/6 patients that were low risk but high likelihood to benefit extended therapy. In total, endocrine therapy treatment decision making aligned with predictive (H/I) results in 93/100 patients. Conclusion: The BCI test was instrumental in assisting almost all women in their decision to receive or maintain adjuvant hormonal therapy and 67% of women discontinued or declined hormonal therapy based on test results. All patients with high risk and high predictive benefit on BCI assay chose to pursue adjuvant endocrine therapy. Oncologists can use BCI in their algorithms of delivering personalized cancer care. Citation Format: Link JS, Buck LJ, Kapoor NS. The breast cancer index as a tool in decision making for adjuvant hormonal therapy in early luminal breast cancer: Initiation, withdrawal and continuance. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-10.

Background monarchE is a phase 3, open-label study evaluating abemaciclib combined with endocrine therapy (ET) compared to ET alone in patients with node positive, HR+, HER2-, high risk early breast cancer (EBC) that resulted in a statistically significant improvement in invasive disease-free survival (IDFS) at a pre-planned interim analysis. Following the positive interim analysis, patients continued to be followed for IDFS, distant recurrence, and overall survival. Methods After surgery and, as indicated, radiotherapy and/or chemotherapy, 5,637 patients with HR+, HER2-, high risk EBC were randomized (1:1) to standard of care adjuvant ET with or without abemaciclib (150 mg BD for 2 years). Patients with ≥4 positive nodes, or 1-3 nodes and either grade 3 disease, tumor size ≥5 cm, or central Ki-67 ≥20% were eligible. Here we present results of the primary outcome IDFS analysis which was planned after approximately 390 IDFS events. Results At the primary outcome analysis, median follow-up was approximately 19 months in both arms (an increase of 3.5 months from the interim analysis). A total of 1437 (25.5%) patients had completed the 2-year treatment period; 3281 (58.2%) were still in the 2-year treatment period. With 395 IDFS events observed in the intent-to-treat population, abemaciclib plus ET continued to demonstrate superior IDFS versus ET alone, with a 28.7% reduction in the risk of developing invasive disease (p=.0009; HR = 0.713; 95% CI = 0.583, 0.871). Two-year IDFS rates were 92.3% in the abemaciclib plus ET arm and 89.3% in the ET alone arm. There was a consistent benefit of abemaciclib in all prespecified subgroups. The addition of abemaciclib to ET also resulted in an improvement in distant relapse-free survival (DRFS). Overall survival was immature at the time of analysis. A key secondary endpoint was efficacy in patients with centrally assessed high Ki-67 (≥20%) (Ki-67H) (n=2498). Disease characteristics were well balanced between the arms of this population. Abemaciclib plus ET demonstrated superior IDFS vs ET alone, with a 30.9% reduction in risk of developing invasive disease (p=.0111; HR = 0.691; 95% CI = 0.519, 0.920) and 2-year IDFS rates of 91.6% and 87.1%, respectively. An improvement in DRFS treatment effect was also observed in the Ki-67H population. At the time of data cutoff, the median treatment duration of abemaciclib was 17.3 months and the median duration of ET was balanced between the arms (18.3 months in the abemaciclib arm and 18.7 months in the ET alone arm). Safety was consistent with the results at the interim IDFS analysis and with the known safety profile of abemaciclib. Conclusions At the primary outcome analysis, with a median follow-up of approximately 19 months, abemaciclib combined with ET continued to demonstrate a clinically meaningful improvement in IDFS in patients with HR+, HER2-, node-positive, high risk, EBC with a statistically significant improvement in IDFS in patients with central Ki-67 ≥20%. ClinicalTrials.gov: NCT03155997 Table 1: PrimaryOutcome EfficacyIntent-to-Treat PopulationIntent-to-Treat PopulationKi-67 ≥20% (Ki-67H) PopulationKi-67 ≥20% (Ki-67H) PopulationEndpointAbemaciclib + ET N=2808ET alone N=2829Abemaciclib + ET N=1262ET alone N=1236IDFS# events, n (%)163 (5.8)232 (8.2)82 (6.5)115 (9.3)log rank P value, HR (95% CI)p=.0009 0.713 (0.583, 0.871)p=.0111 0.691 (0.519, 0.920)Rate (%) at 2 years (95% CI)92.3 (90.9, 93.5)89.3 (87.7, 90.7)91.6 (89.4, 93.4)87.1 (84.3, 89.5)Difference (%) in 2-year rates (95% CI)3 (1.1, 5.0)4.5 (1.2, 7.7)DRFS# events, n (%)131 (4.7)193 (6.8)65 (5.2)102 (8.3)log rank P value, HR (95% CI)p=.0009 0.687 (0.551, 0.858)0.609 (0.445, 0.833)Rate (%) at 2 years (95% CI)93.8 (92.6, 94.9)90.8 (89.3, 92.1)93.6 (91.6, 95.1)88.5 (85.7, 90.7)Difference (%) in 2-year rates (95%CI)3 (1.2, 4.8)5.1 (2.1, 8.1) Citation Format: Joyce A. O'Shaughnessy, Stephen Johnston, Nadia Harbeck, Masakazu Toi, Young-Hyuck Im, Mattea Reinisch, Zhimin Shao, Pirkko Liisa Kellokumpu Lehtinen, Chiun-Sheng Huang, Alexey Tryakin, Matthew Goetz, Hope S Rugo, Elzbieta Senkus, Laura Testa, Michael Andersson, Kenji Tamura, Guenther G. Steger, Lucia Del Mastro, Joanne Cox, Tammy Forrester, Sarah Sherwood, Xuelin Li, Ran Wei, Miguel Martin, Priya Rastogi. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early 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 GS1-01.

Cancer-specific utility instrument for health economic evaluations: A synopsis of the EORTC QLU-C10D user manual and current validity evidence.

Background: Adjuvant endocrine therapy (ET) in ER+ breast cancer (BC) reduces local, distant, and contralateral BC events and improves overall survival (OS). Furthermore, decreased adherence or omission of ET increases the risk of death. However, in ER+ pts with early-stage BC treated with NAC who have a pathologic complete response (pCR), the importance of adjuvant ET may be called into question. We sought to examine the impact of ET omission on the survival of pts with ER+ BC treated with NAC, according to pCR vs residual disease. Methods: We queried the National Cancer Database (NCDB) 2010-2018 for female pts with stage I-III ER+ BC treated with NAC followed by surgery. pCR was defined as ypT0/ypTis, ypN0. The percent receiving adjuvant ET and the impact of adjuvant ET omission on overall survival (OS) in patients with and without pCR were assessed separately based on HER2 expression. OS was analyzed with adjuvant ET as a time-dependent covariate using Cox proportional hazards regression. Results: We identified 34,394 pts treated with NAC for ER+ BC (28,434 ER+/HER2-, 5960 ER+/HER2+). Pts with ER+/HER2+ BC were less likely than pts with ER+/HER2- BC to have received adjuvant ET (61.6% vs 88.8%, p< 0.001). Overall, 4505 (13.1%) had pCR (9.1% of ER+/HER2- and 32.0% of ER+/HER2+). Within each subtype, pts with pCR were significantly less likely to start adjuvant ET after surgery than pts with residual disease (78.4% vs 89.8% for ER+/HER2- and 46.5% vs 68.7% for ER+/HER2+, each p< 0.001), Table 1. Regarding those with residual disease, pts with ER+/HER2+ BC were less likely than ER+/HER2- BC to receive adjuvant ET (68.7% vs 89.8%, p< 0.001). Median follow-up was 4.4 years. Among pts with pCR, 5-year OS was 93.2% (95% CI: 92.1-94.4%) for ER+/HER2- BC and 94.3% (95% CI: 93.1-95.5%) for ER+/HER2+ BC (p=0.08), while among patients with residual disease 5-year OS was 81.7% (95% CI: 81.1-82.2%) and 85.7% (95% CI: 84.5-86.9%) for the two subtypes respectively (p< 0.001). On multivariable analysis, omission of adjuvant ET was significantly associated with poorer OS in patients with residual disease for both ER+/HER2- BC (adjusted HR 1.72, p< 0.001) and ER+/HER2+ BC (adjusted HR 1.63, p< 0.001). In contrast, omission of adjuvant ET was not significantly associated with OS in patients with pCR, regardless of HER2 status (ER+/HER2- adjusted HR 1.28, p=0.20; ER+/HER2+ adjusted HR 1.13, p=0.54), Table 1. Conclusions: In pts receiving NAC for ER+ BC, those with ER+/HER2+ disease were less likely to have received adjuvant ET compared to ER+/HER2- patients, regardless of pCR. In pts with residual disease after NAC, omission of adjuvant ET was associated with significantly higher risk of death. These data provide strong support for interventions to increase utilization of ET, especially for patients with residual disease following NAC. The observation that ET omission did not impact OS in pts with ER+ BC who achieve pCR following NAC is hypothesis generating and may have implications for future de-escalation trials for this subset of patients. Table 1. Differential use of adjuvant endocrine therapy by subtype and pCR and the impact on overall survival Citation Format: Grace M. Choong, Judy C. Boughey, Tanya L. Hoskin, Courtney N. Day, Matthew P. Goetz. Impact of adjuvant endocrine therapy (ET) omission in ER+ breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) [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 P2-03-12.

Hormone therapy for early prostate cancer has demonstrated an improvement in clinical and pathological variables, but not always an improvement in overall survival. We performed a systematic review of both adjuvant and neo-adjuvant hormone therapy combined with surgery or radiotherapy in localised or locally advanced prostate cancer. The objective of this review was to undertake a systematic review and, if possible, a meta-analysis of neo-adjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer. We searched MEDLINE (1966-2006), EMBASE, The Cochrane Library, Science Citation Index, LILACS, and SIGLE for relevant randomised trials. Handsearching of appropriate publications was also undertaken. Randomised or quasi-randomised controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1-T4, any N, M0, comparing neo-adjuvant or adjuvant hormonal deprivation in combination with primary therapy (radical radiotherapy or radical prostatectomy) versus primary therapy alone were included in this review. Data were extracted from eligible studies and assessed for quality, and included information on study design, participants, interventions, and outcomes. Comparable data were pooled together for meta-analysis with intention-to treat principle. Men with prostate cancer have different clinical outcomes based on their risk (T1-T2, T3-T4, PSA levels and Gleason score). However, the majority of studies included in this review did not report results by risk groups; therefore, it was not possible to perform sub-group analysis. Neo-adjuvant hormonal therapy prior to prostatectomy did not improve overall survival (OR 1.11, 95% CI 0.67 to 1.85, P = 0.69). However, there was a significant reduction in the positive surgical margin rate (OR 0.34, 95% CI 0.27 to 0.42, P < 0.00001) and a significant improvement in other pathological variables such as lymph node involvement, pathological staging and organ confined rates. There was a borderline significant reduction of disease recurrence rates (OR 0.74, 95% CI 0.55 to 1.0, P = 0.05), in favour of treatment. The use of longer duration of neo-adjuvant hormones, that is either 6 or 8 months prior to prostatectomy, was associated with a significant reduction in positive surgical margins (OR 0.56, 95% CI 0.39 to 0.80, P = 0.002). In one study, neo-adjuvant hormones prior to radiotherapy significantly improved overall survival for Gleason 2 to 6 patients; although, in two studies, there was no improvement in disease-specific survival (OR 0.99, 95% CI 0.75 to 1.32, P = 0.97). However, there was a significant improvement in both clinical disease-free survival (OR 1.86, 95% CI 1.93 to 2.40, P < 0.00001) and biochemical disease-free survival (OR 1.93, 95% CI 1.45 to 2.56, P < 0.00001). Adjuvant androgen deprivation following prostatectomy did not significantly improve overall survival at 5 years (OR 1.50, 95% CI 0.79 to 2.85, P = 0.2); although one study reported a significant disease-specific survival advantage with adjuvant therapy (P = 0.001). In addition, there was a significant improvement in disease-free survival at both 5 years (OR 3.73, 95%CI 2.30 to 6.03, P < 0.00001) and 10 years (OR 2.06, 95% CI 1.34 to 3.15, P = 0.0009). Adjuvant therapy following radiotherapy resulted in a significant overall survival gain apparent at 5 (OR 1.46, 95% CI 1.17 to 1.83, P = 0.0009) and 10 years (OR 1.44, 95% CI 1.13 to 1.84, P = 0.003); although there was significant heterogeneity (P = 0.09 and P = 0.07, respectively). There was also a significant improvement in disease-specific survival (OR 2.10, 95% CI 1.53 to 2.88, P = 0.00001) and disease-free survival (OR 2.53, 95% CI 2.05 to 3.12, P < 0.00001) at 5 years. Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. Significant local control may be achieved when given prior to prostatectomy or radiotherapy, which may improve patient's quality of life. When given adjuvant to these primary therapies, hormone therapy, not only provides a method for local control, but there is also evidence for a significant survival advantage. However, hormone therapy is associated with significant side effects, such as hot flushes and gynaecomastia, as well as cost implications. The decision to use hormone therapy should, therefore, be taken at a local level, between the patient, clinician and policy maker, taking into account the clinical benefits, toxicity and cost. More research is needed to guide the choice, the duration, and the schedule of hormonal deprivation therapy, and the impact of long-term hormone therapy with regard to toxicity and the patient's quality of life.

Background: Currently, the standard immunotherapy treatment for anti-programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer is a combination of PD-L1 antibody and nab-paclitaxel. PD-1/PD-L1 antibody was investigated as a treatment for hormone receptor positive (HR+) breast cancer; however, the efficacy of single agents is poor. In pre-clinical studies, anti-PD-1/PD-L1 antibody, CDK4/6 inhibitors, and endocrine therapy (ET) have synergistic effects. We initiated this investigator-initiated trial to evaluate the efficacy and safety of the combination of nivolumab, abemaciclib, and ET (fulvestrant [FUL] or letrozole [LET]) as a first- or second-line treatment for patients (pts) with HR+, human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). Methods: This multicenter, multi-cohort, nonrandomized, open-label phase II study evaluated the efficacy and safety of nivolumab, abemaciclib, and ET (FUL or LET) in pts with HR+, HER2- MBC. Key eligibility criteria for the FUL cohort were: HR+, HER2- MBC with ECOG PS ≤ 1; measurable disease; no more than one ET; no prior chemotherapy for MBC; and had exhibited disease progression while receiving ET, adjuvant ET, or ≤ 12 months after adjuvant ET. Key eligibility criteria for the LET cohort were: postmenopausal HR+, HER2- MBC with ECOG PS ≤ 1; measurable disease; and no prior systemic therapy. ET as an adjuvant was permitted if the patient had a disease-free interval &amp;gt; 12 months after the completion of ET. Patients received 240 mg nivolumab on days 1 and 15, 150 mg abemaciclib twice daily, and either 500 mg FUL on days 1, 15, 29, and every 4 weeks thereafter (FUL cohort) or 2.5 mg LET once daily (LET cohort) until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Key secondary endpoints included toxicity, disease control rate (DCR: CR+PR+SD), progression-free survival (PFS), and the overall survival (OS). The threshold and expected ORR of the FUL cohort were 45% and 60%, respectively; and 32 pts would ensure a statistical power of 80% (α = 0.20). The threshold and expected ORR of the LET cohort were 55% and 75%, respectively; and 16 pts would ensure a statistical power of 80% (α = 0.20). Results: Between June and December 2019, 17 pts were enrolled (FUL cohort: n = 12, LET cohort: n = 5). One patient in the FUL cohort was excluded due to prior treatment history. Enrollment was closed and combination treatment was discontinued mid-study due to safety concerns. All pts had ≥ 1 adverse event (AE). AEs ≥ Grade 3 were observed in 91.7% and 100% of pts in the FUL and LET cohorts, respectively. Immune-related AEs ≥ Grade 3 were observed in 66.7% and 60.0% of pts in the FUL and LET cohorts, respectively. The most frequent AEs ≥ Grade 3 were elevated liver function tests (LFT; FUL cohort: 50.0%, LET cohort: 60.0%). Immune-related (elevated LFT) AEs ≥ Grade 3 were observed in 50.0% and 40.0% of pts in the FUL and LET cohorts, respectively. Severe AEs (SAEs) were observed in 50.0% and 60.0% of pts in the FUL and LET cohorts, respectively. One treatment-related patient death occurred in the LET cohort due to interstitial lung disease (ILD). ORR was 54.5% (6/11) and 20% (1/5) in the FUL and LET cohorts, respectively. DCR was 90.9% (10/11) in the FUL cohort and 80.0% (4/5) in the LET cohort. Due to the discontinuation, PFS and OS were undetermined. Conclusions: Although nivolumab + abemaciclib + FUL appeared to have activity, our findings do not support further investigation of this combination therapy due to toxicity. Toxicity profiles vary with CDK4/6 inhibitors; therefore, a different inhibitor may improve tolerability. Results of the ongoing nivolumab, palbociclib, and ET trial are awaited (CheckMate 7A8, NCT04075604). Clinical trial information: JapicCTI-194782. Citation Format: Jun Masuda, Junji Tsurutani, Norikazu Masuda, Yuko Tanabe, Tsutomu Iwasa, Masato Takahashi, Manabu Futamura, Koji Matsumoto, Kenjiro Aogi, Hiroji Iwata, Mari Hosonaga, Toru Mukohara, Kenichi Yoshimura, Toshimi Takano. Phase II study of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR+, HER2- metastatic breast cancer: WJOG11418B NEWFLAME trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-10.

Background: The study examined the correlations among the results of the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire, Core 30 (QLQ-C30) completed by elderly cancer patients and their family caregivers and the Eastern Cooperative Oncology Group (ECOG)-performance status (PS) evaluated by medical doctors. Methods: The study sample included 269 persons with cancer aged 55 years or older and their family care- givers recruited from hospitals located in Seoul and Gyeonggi-do. The results of the ECOG-PS evaluated by medical doctors were obtained from medical records. Intra-class correlation analysis was used to assess rater reliability between the elderly cancer patients and their family caregivers. Correlations among the EORTC QLQ-C30 and the ECOG-PS were tested using the Kruskal-Wallis test and Spearmen's correlation. Results: The results showed that four subscales of quality of life (physical functioning, emotional functioning, social functioning, and global health status) and three items under symptoms (fatigue, pain, and financial diffi- culties) in the EORTC QLQ-C30 were highly consistent between patients and their family caregivers. From the EORTC QLQ-C30 results, social functioning, role functioning, health status, fatigue, pain, and appetite loss (patients results) and physical functioning (family caregivers results) were highly consistent with the results of the ECOG-PS by the physicians. Conclusions: The findings suggest that when the older persons with cancer have difficulty expressing their own thoughts or feelings, the EORTC QLQ-C30 completed by their family caregivers and the results of the ECOG-PS completed by the physicians could be used as substitutes.

Existing international data has shown that glioma patients suffer from poorer health-related quality of life (HRQoL). The European Organization for Research and Treatment of Cancer (EORTC) brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) was developed to be together with EORTC Core Quality of Life Questionnaire (QLQ-C30) for cancer patients, highlighting issues particularly relevant to brain tumor patients. It has since been translated and validated across numerous cohorts. However, its psychometric properties have yet to be examined in Singapore. This study aimed to validate the use of QLQ-BN20 in a nationally representative sample of glioma patients in Singapore. Eighty-seven patients who had undergone neurosurgery for glioma from six hospitals in Singapore completed three self-reported measures of HRQoL (the EuroQol EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-BN20). Descriptive statistics summarized their characteristics and scores on the questionnaires. Psychometric properties of QLQ-BN20 examined included convergent and discriminant validity, internal consistency (Cronbach's alpha), and construct validity (Spearman's correlation). Clinical validity of QLQ-BN20 was determined based on whether QLQ-BN20 scores could differentiate patients with good and poor functional status as measured by Karnofsky Performance Scale and Barthel's Index. The QLQ-BN20 was demonstrated to have good convergent validity (item-own scale correlation >0.70) and discriminant validity (item-own scale correlation higher than item-other scale correlation). There is high internal consistency, both overall (α=0.88) and within multi-item subscales (α=0.74-0.88). Conceptually similar subscales between different tools were more strongly correlated. For instance, the QLQ-C30 physical functioning subscale and the QLQ-BN20 motor dysfunction subscale (r=-0.65, P<0.001), and the QLQ-C30 cognitive functioning subscale and the QLQ-BN20 cognitive deficits subscale (r=-0.51, P<0.001). QLQ-BN20 was also able to distinguish between functional statuses of patients (P<0.05). This study supports the validity and reliability of the EORTC QLQ-BN20 among patients with glioma in Singapore. There is good convergent and discriminant validity, internal consistency, construct validity, and clinical validity. The QLQ-BN20 is a valuable supplement to the QLQ-C30. Hence, we recommend expanding its use for all glioma patients and possibly brain cancer patients in Singapore.

PurposePhysical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library.MethodsThe 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated.ResultsThe QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe).ConclusionThe modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML.

Endocrine therapy (ET) is a cornerstone in adjuvant therapy for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer. However, recent research challenges the conventional 5-year adjuvant therapy duration. Patients with T1N0M0 HR+/HER2− breast cancer face a 13% risk of distant recurrence after 5 years of endocrine treatment. This risk increases to 34% over two decades for patients with 4–9 lymph node metastases. Thus, it is important to consider supplementary treatments for T1N0M0 HR+/HER2− breast cancer patients, particularly those with additional high-risk features such as young age, high tumor grade, or adverse genomic profile. We summarize intensive treatment methods for T1N0M0 HR+/HER2− breast cancer patients, which extend beyond the standard 5-year tamoxifen (TAM)-based adjuvant ET. These methods include intensive ET, poly(ADP-ribose) polymerase (PARP) inhibitors, other targeted therapies, antibody-drug conjugates, oral chemotherapy, immunotherapy, and enhanced prevention of bone metastasis. This review provides a foundation for developing personalized adjuvant treatment strategies for patients with T1N0M0 HR+/HER2− breast cancer.