Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer.

BACKGROUND: The addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvant and adjuvant therapy. The primary results regarding event-free survival in this trial have not been reported. METHODS: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response (the results for which have been reported previously) and event-free survival, defined as the time from randomization to the date of disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause. Safety was also assessed. RESULTS: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. The median follow-up at this fourth planned interim analysis (data cutoff, March 23, 2021) was 39.1 months. The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy. CONCLUSIONS: In patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).

Analysis of simplicial complexes to determine when to sample for quantitative DCE MRI of the breast.

PURPOSE: A method is presented to select the optimal time points at which to measure DCE-MRI signal intensities, leaving time in the MR exam for high-spatial resolution image acquisition. THEORY: Simplicial complexes are generated from the Kety-Tofts model pharmacokinetic parameters Ktrans and ve . A geometric search selects optimal time points for accurate estimation of perfusion parameters. METHODS: The DCE-MRI data acquired in women with invasive breast cancer (N = 27) were used to retrospectively compare parameter maps fit to full and subsampled time courses. Simplicial complexes were generated for a fixed range of Kety-Tofts model parameters and for the parameter ranges weighted by estimates from the fully sampled data. The largest-area manifolds determined the optimal three time points for each case. Simulations were performed along with retrospectively subsampled data fits. The agreement was computed between the model parameters fit to three points and those fit to all points. RESULTS: The optimal three-point sample times were from the data-informed simplicial complex analysis and determined to be 65, 204, and 393 s after arrival of the contrast agent to breast tissue. In the patient data, tumor-median parameter values fit using all points and the three selected time points agreed with concordance correlation coefficients of 0.97 for Ktrans and 0.67 for ve . CONCLUSION: It is possible to accurately estimate pharmacokinetic parameters from three properly selected time points inserted into a clinical DCE-MRI breast exam. This technique can provide guidance on when to capture images for quantitative data between high-spatial-resolution DCE-MRI images.

Quantitative multiparametric MRI predicts response to neoadjuvant therapy in the community setting.

BACKGROUND: The purpose of this study was to determine whether advanced quantitative magnetic resonance imaging (MRI) can be deployed outside of large, research-oriented academic hospitals and into community care settings to predict eventual pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with locally advanced breast cancer. METHODS: Patients with stage II/III breast cancer (N = 28) were enrolled in a multicenter study performed in community radiology settings. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI data were acquired at four time points during the course of NAT. Estimates of the vascular perfusion and permeability, as assessed by the volume transfer rate (Ktrans) using the Patlak model, were generated from the DCE-MRI data while estimates of cell density, as assessed by the apparent diffusion coefficient (ADC), were calculated from DW-MRI data. Tumor volume was calculated using semi-automatic segmentation and combined with Ktrans and ADC to yield bulk tumor blood flow and cellularity, respectively. The percent change in quantitative parameters at each MRI scan was calculated and compared to pathological response at the time of surgery. The predictive accuracy of each MRI parameter at different time points was quantified using receiver operating characteristic curves. RESULTS: Tumor size and quantitative MRI parameters were similar at baseline between groups that achieved pCR (n = 8) and those that did not (n = 20). Patients achieving a pCR had a larger decline in volume and cellularity than those who did not achieve pCR after one cycle of NAT (p < 0.05). At the third and fourth MRI, changes in tumor volume, Ktrans, ADC, cellularity, and bulk tumor flow from baseline (pre-treatment) were all significantly greater (p < 0.05) in the cohort who achieved pCR compared to those patients with non-pCR. CONCLUSIONS: Quantitative analysis of DCE-MRI and DW-MRI can be implemented in the community care setting to accurately predict the response of breast cancer to NAT. Dissemination of quantitative MRI into the community setting allows for the incorporation of these parameters into the standard of care and increases the number of clinical community sites able to participate in novel drug trials that require quantitative MRI.

Real-world survival outcomes of heavily pretreated patients with refractory HR+, HER2-metastatic breast cancer receiving single-agent chemotherapy-a comparison with MONARCH 1.

PURPOSE: In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. METHODS: The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. CONCLUSIONS: This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.

Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer.

PURPOSE: The effects of chemotherapy dose intensity on survival in patients with advanced non-small-cell lung cancer (NSCLC) are poorly understood. We retrospectively analyzed dose delays/reduction, relative dose intensity (RDI), and the association between chemotherapy intensity and survival in advanced NSCLC. METHODS: This retrospective cohort study included adults with advanced lung cancer who received first-line myelosuppressive platinum-based chemotherapy (January 2007-December 2010) in ~ 230 US Oncology Network community practices. Dose delays ≥ 7 days, dose reductions ≥ 15%, and RDI relative to standard regimens were described. Overall survival (OS) was measured using Kaplan-Meier and Cox proportional hazard (PH) models. RESULTS: Among 3866 patients with advanced NSCLC, 32.4% experienced dose delays ≥ 7 days, 50.1% experienced dose reductions ≥ 15%, and 40.4% had RDI < 85%. Reduced RDI was also common regardless of baseline ECOG PS (ECOG PS ≥ 2, 56.2%; ECOG PS 0, 33.6%) and tumor subgroup (squamous cell carcinoma, 52.2%; adenocarcinoma, 36.0%). When stratified by chemotherapy intensity measures, significant OS differences were observed only for dose delays. Median (95% CI) OS was 1.02 years (0.96-1.12) for dose delays ≥ 7 days and 0.71 years (0.66-0.77) for dose delays < 7 days. In multivariable Cox PH analysis, dose delays ≥ 7 days (HR = 0.71; 95% CI = 0.63-0.80) and RDI ≥ 85% (HR = 1.18; 95% CI = 1.05-1.32) were significantly associated with decreased mortality. CONCLUSIONS: Dose delays, dose reductions, and reduced RDI were common, and dose delays ≥ 7 days and high RDI were significantly associated with decreased mortality. These results can help identify potential risk factors and characterize the effect of chemotherapy dose modification strategies on mortality.

Repeatability, reproducibility, and accuracy of quantitative mri of the breast in the community radiology setting.

BACKGROUND: Quantitative diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) have the potential to impact patient care by providing noninvasive biological information in breast cancer. PURPOSE/HYPOTHESIS: To quantify the repeatability, reproducibility, and accuracy of apparent diffusion coefficient (ADC) and T1 -mapping of the breast in community radiology practices. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Ice-water DW-MRI and T1 gel phantoms were used to assess accuracy. Normal subjects (n = 3) and phantoms across three sites (one academic, two community) were used to assess reproducibility. Test-retest analysis at one site in normal subjects (n = 12) was used to assess repeatability. FIELD STRENGTH/SEQUENCE: 3T Siemens Skyra MRI quantitative DW-MRI and T1 -mapping. ASSESSMENT: Quantitative DW-MRI and T1 -mapping parametric maps of phantoms and fibroglandular and adipose tissue of the breast. STATISTICAL TESTS: Average values of breast tissue were quantified and Bland-Altman analysis was performed to assess the repeatability of the MRI techniques, while the Friedman test assessed reproducibility. RESULTS: ADC measurements were reproducible across sites, with an average difference of 1.6% in an ice-water phantom and 7.0% in breast fibroglandular tissue. T1 measurements in gel phantoms had an average difference of 2.8% across three sites, whereas breast fibroglandular and adipose tissue had 8.4% and 7.5% average differences, respectively. In the repeatability study, we found no bias between first and second scanning sessions (P = 0.1). The difference between repeated measurements was independent of the mean for each MRI metric (P = 0.156, P = 0.862, P = 0.197 for ADC, T1 of fibroglandular tissue, and T1 of adipose tissue, respectively). DATA CONCLUSION: Community radiology practices can perform repeatable, reproducible, and accurate quantitative T1 -mapping and DW-MRI. This has the potential to dramatically expand the number of sites that can participate in multisite clinical trials and increase clinical translation of quantitative MRI techniques for cancer response assessment. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Use of Tokens to Unlock Greater Data Sharing in Health Care.

This Viewpoint discusses the use of privacy-preserving record linkage, a token-based record linkage system, as a promising avenue for building a data infrastructure system that bridges isolated data.

The treatment patterns, efficacy, and safety of nab (®)-paclitaxel for the treatment of metastatic breast cancer in the United States: results from health insurance claims analysis.

BACKGROUND: nab-Paclitaxel is an albumin-bound formulation of paclitaxel approved for the treatment of metastatic breast cancer (MBC). This analysis was designed to characterize the treatment patterns, efficacy, and safety of nab-paclitaxel for MBC treatment using health claims data from US health plans associated with Optum. METHODS: Women aged ≥ 18 years who initiated nab-paclitaxel for MBC treatment from January 1, 2005, to September 30, 2012, and who met eligibility criteria were selected from the Optum Research Database for this analysis. Patients were required to have complete medical coverage and pharmacy benefits, ≥ 6 months of continuous enrollment, and a diagnosis of MBC prior to nab-paclitaxel initiation. The pattern of use for nab-paclitaxel (eg, regimen, schedule, duration, and administration) and claims-captured toxicities were characterized by line of therapy. Overall survival (OS) and time to next therapy or death (TNTD) were described by line of therapy, regimen, and schedule. RESULTS: Of the 664 nab-paclitaxel patients, 172 (25.9%) received it as first-line therapy, 211 (31.8%) as second-line therapy, and 281 (42.3%) as third-line or later therapy. Overall, the majority of patients received monotherapy (61%) and followed a weekly (71%) rather than an every 3 weeks treatment schedule. nab-Paclitaxel was often (31.7%) combined with targeted therapy (57.5% with bevacizumab and 23.9% with trastuzumab or lapatinib). The median duration of therapy was 128 days (4.2 months). For the overall population, median OS was 17.4 months (22.7, 17.4, and 15.1 months in first-, second-, and third-line or later therapy, respectively). Median TNTD was 6.1 months (7.1, 6.6, and 5.3 months in first-, second-, and third-line or later therapy, respectively). For patients aged ≤ 50 years or with ≥ 3 metastatic sites, median OS was 15.6 months. No new safety signal was identified. CONCLUSIONS: In this US healthcare system, the majority of patients received nab-paclitaxel as second-line or later therapy, monotherapy, and weekly treatment. The efficacy and safety outcomes of nab-paclitaxel observed in this real-world setting appear consistent with those from clinical trial data.

Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices.

BACKGROUND: A wide variety of myelosuppressive chemotherapy regimens are used for the treatment of cancer in clinical practice. Neutropenic complications, such as febrile neutropenia, are among the most common side effects of chemotherapy, and they often necessitate delays or reductions in doses of myelosuppressive agents. Reduced relative dose intensity (RDI) may lead to poorer disease-free and overall survival. METHODS: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of adjuvant or neoadjuvant chemotherapy received by patients without metastases who initiated treatment between January 1, 2007, and March 31, 2011. For each regimen, we estimated the incidences of dose delays (≥7 days in any cycle of the course), dose reductions (≥ 15% in any cycle of the course), and reduced RDI (<85% over the course) relative to the corresponding standard tumor regimens described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). RESULTS: This study included 16,233 patients with 6 different tumor types who received 1 of 20 chemotherapy regimens. Chemotherapy dose delays, dose reductions, and reduced RDI were common among patients treated in community oncology practices in the United States, but RDI was highly variable across patients, regimens, and tumor types (0.486-0.935 for standard tumor regimen cohorts). Reduced RDI was more common in older patients, obese patients, and patients whose daily activities were restricted. CONCLUSIONS: In this large evaluation of RDI in US clinical practice, physicians frequently administered myelosuppressive agents at dose intensities lower than those of standard regimens.

Iniparib plus chemotherapy in metastatic triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition. METHODS: We conducted an open-label, phase 2 study to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib, a small molecule with PARP-inhibitory activity, in patients with metastatic triple-negative breast cancer. A total of 123 patients were randomly assigned to receive gemcitabine (1000 mg per square meter of body-surface area) and carboplatin (at a dose equivalent to an area under the concentration-time curve of 2) on days 1 and 8--with or without iniparib (at a dose of 5.6 mg per kilogram of body weight) on days 1, 4, 8, and 11--every 21 days. Primary end points were the rate of clinical benefit (i.e., the rate of objective response [complete or partial response] plus the rate of stable disease for ≥6 months) and safety. Additional end points included the rate of objective response, progression-free survival, and overall survival. RESULTS: The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% (P=0.01) and the rate of overall response from 32% to 52% (P=0.02). The addition of iniparib also prolonged the median progression-free survival from 3.6 months to 5.9 months (hazard ratio for progression, 0.59; P=0.01) and the median overall survival from 7.7 months to 12.3 months (hazard ratio for death, 0.57; P=0.01). The most frequent grade 3 or 4 adverse events in either treatment group included neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level. No significant difference was seen between the two groups in the rate of adverse events. CONCLUSIONS: The addition of iniparib to chemotherapy improved the clinical benefit and survival of patients with metastatic triple-negative breast cancer without significantly increased toxic effects. On the basis of these results, a phase 3 trial adequately powered to evaluate overall survival and progression-free survival is being conducted. (Funded by BiPar Sciences [now owned by Sanofi-Aventis]; ClinicalTrials.gov number, NCT00540358.).

Telemedicine and Burnout-How Enhancing Operational Support Can Improve Digital Health Tools.

ABSTRACT: During the COVID-19 pandemic, there was an unprecedented growth in telemedicine due to the need to provide safe access to care during a global pandemic. The regulatory, compliance, and payment policy landscape favorably changed, paving the way for growth in utilization. Despite these favorable changes in the landscape, operational and technical burdens remained barriers to optimal use of telemedicine. Investments in operational processes and vendor selection can improve the patient and clinician experience in using telemedicine, so this digital tool can diminish burnout.

Oncology comparative effectiveness research: a multistakeholder perspective on principles for conduct and reporting.

Comparative effectiveness research (CER) can assist patients, clinicians, purchasers, and policy makers in making more informed decisions that will improve cancer care and outcomes. Despite its promise, the factors that distinguish CER from other types of evidence remain mysterious to many oncologists. One concern is whether CER studies will improve decision making in oncology or only add to the massive amount of research information that decision makers must sift through as part of their professional responsibilities. In this report, we highlight several issues that distinguish CER from the most common way evidence is generated for cancer therapy-phase I-III clinical trials. To identify the issues that are most relevant to busy decision makers, we assembled a panel of active professionals with a wide range of roles in cancer care delivery. This panel identified five themes that they considered most important for CER in oncology, as well as fundamental threats to the validity of individual CER studies-threats they termed the "kiss of death" for their applicability to practice. In discussing these concepts, we also touched upon the notion of whether cancer is special among health issues with regard to how evidence is generated and used.

Cancer Informatics 2023: Data Sharing and Federating Learning Point Towards New Collaborative Opportunities.

OBJECTIVE: To summarize significant research contributions on cancer informatics published in 2022. METHODS: An extensive search using PubMed/MEDLINE was conducted to identify the scientific contributions published in 2022 that address topics in cancer informatics. The selection process comprised three steps: (i) ten candidate best papers were first selected by the two section editors, (ii) external reviewers from internationally renowned research teams reviewed each candidate best paper, and (iii) the final selection of three best papers was conducted by the editorial board of the Yearbook. RESULTS: The three selected best papers demonstrate advances in federated learning, drug synergy prediction, and utilization of clinical note data. CONCLUSION: Cancer informatics continues to mature as a subfield of biomedical informatics. Applications of informatics methods to data sharing and federated approaches are especially notable in 2022.

Patient-Reported Outcomes, Digital Health, and the Quest to Improve Health Equity.

The theme of the 2023 American Society of Clinical Oncology Annual Meeting is Partnering With Patients: The Cornerstone of Cancer Care and Research. As we aim to partner with patients to improve their health care, digital tools have the potential to enhance patient-centered cancer care and make clinical research more accessible and generalizable. Using electronic patient-reported outcomes (ePROs) to collect patients' reports of symptoms, functioning, and well-being facilitates patient-clinician communication and improves care and outcomes. Early studies suggest that racial and ethnic minority populations, older patients, and patients with less education may benefit even more from ePRO implementation. Clinical practices looking to implement ePROs can refer to the resources of the PROTEUS Consortium (Patient-Reported Outcomes Tools: Engaging Users & Stakeholders). Beyond ePROs, in response to the COVID-19 pandemic, cancer practices have rapidly adopted other digital tools (eg, telemedicine, remote patient monitoring). As implementation grows, we must be aware of the limitations of these tools and implement them in ways to promote optimal function, access, and ease of use. Infrastructure, patient, provider, and system-level barriers need to be addressed. Partnerships across all levels can inform development and implementation of digital tools to meet the needs of diverse groups. In this article, we describe how we use ePROs and other digital health tools in cancer care, how digital tools can expand access to and generalizability of oncology care and research, and prospects for broader implementation and use.

Tenets for Implementing Electronic Patient-Reported Outcomes for Remote Symptom Monitoring During Cancer Treatment.

PURPOSE: Symptoms are common in patients receiving systemic treatment for metastatic cancer. Monitoring patients with electronic patient-reported outcomes (ePROs) detects severe and worsening symptoms early, enabling care teams to intervene and prevent downstream complications and thereby improving outcomes. The Centers for Medicare & Medicaid Services will require patient-reported outcome (PRO) monitoring in the upcoming Enhancing Oncology Model, and many practices will likely attempt to implement PROs in patient care for the first time. METHODS: To assist practices with the design and implementation of ePRO remote symptom monitoring programs, tenets were drawn from prior ePRO program experiences and research. RESULTS: Successful implementation requires a quality improvement approach to change management with attention to software functionality, measured outcomes, personnel deployment, leadership and culture, workflow, equity, and patient engagement. Specific approaches in each of these areas can optimize program participation and effectiveness. Continuous program monitoring to identify and address barriers is essential to success. Initial challenges with personnel acceptance and patient participation are common and can be overcome by using these tenets. CONCLUSION: Remote symptom monitoring with ePROs is a key component of quality cancer care and population health management that requires organizational commitment and a deliberate approach by practices using established tenets to assure successful implementation.

Impact of Remote Symptom Monitoring With Electronic Patient-Reported Outcomes on Hospitalization, Survival, and Cost in Community Oncology Practice: The Texas Two-Step Study.

PURPOSE: There is raising interest to implement electronic patient-reported outcomes (ePROs) for symptom monitoring to enhance the quality of cancer care. Step 1 of the Texas Two-Step Study demonstrated successful implementation of an ePRO system in >200 sites of service of a large community oncology practice. We now report step 2 of this study which evaluates the impact of ePROs on outcomes among patients enrolled in the Centers for Medicare & Medicaid Services' Oncology Care Model (OCM) program. METHODS: This observational study focused on patients with metastatic cancer enrolled in OCM at large community oncology practice located in Texas between July 2020 and December 2020. Patients who completed ≥1 survey via the ePRO tool were included in the study group and were propensity score matched with patients in a control group. Adverse events (AEs; hospitalizations, emergency department visits, deaths) and total cost of care were a priori study outcomes. Mann-Whitney U and chi-square tests compared continuous and categorical variables, respectively, with multivariable logistic regression for adjustment of covariates. RESULTS: Of 831 patients with metastatic cancer, 458 matched patients (229/group) were identified, with 52% male and a mean age of 74 years. Mean total AEs were lower in the study group compared with control (0.98 v 1.41; P = .007), with decreased hospitalizations (20% v 32.5%; P = .002), emergency visits (38.4% v 42.3%; P > .05), and deaths (11.8% v 16.6%; P > .05). Average number of hospitalizations was lower (0.28 v 0.52; P = .003) with reduced mean duration of hospitalizations (1.9 vs 3.2 d; P = .03). The total cost of care was reduced by an average of $1,146 per member per month. CONCLUSION: Symptom monitoring with ePROs improved quality and value of cancer care delivery by reducing hospitalizations, emergency visits, and deaths while lowering cost of care in a large oncology practice.

Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: ExteNET showed that neratinib, an irreversible pan-HER tyrosine kinase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET. METHODS: In this international, randomised, double-blind, placebo-controlled, phase 3 trial, women aged 18 years or older with stage 1-3c (amended to stage 2-3c) HER2-positive breast cancer who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab were eligible. Patients were randomly assigned to oral neratinib 240 mg/day or placebo for 1 year. Randomisation was stratified according to hormone receptor (HR) status (HR-positive vs. HR-negative), nodal status (0, 1-3 or 4+), and trastuzumab regimen (sequentially vs. concurrently with chemotherapy). Overall survival was analysed by intention to treat. ExteNET is registered (Clinicaltrials.gov: NCT00878709) and is complete. RESULTS: Between July 9, 2009, and October 24, 2011, 2840 women received neratinib (n = 1420) or placebo (n = 1420). After a median follow-up of 8.1 (IQR, 7.0-8.8) years, 127 patients (8.9%) in the neratinib group and 137 patients (9.6%) in the placebo group in the intention-to-treat population had died. Eight-year overall survival rates were 90.1% (95% CI 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75-1.21; p = 0.6914). CONCLUSIONS: Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2-positive breast cancer.

Cancer Informatics 2022: Real-World Data Yields Important Insights into the Conduct of Clinical Trials and Registries.

OBJECTIVE: To summarize significant research contributions on cancer informatics published in 2021. METHODS: An extensive search using PubMed/MEDLINE and Altmetric scores was conducted to identify the scientific contributions published in 2021 that address topics in cancer informatics. The selection process comprised three steps: (i) 15 candidate best papers were first selected by the two section editors, (ii) external reviewers from internationally renowned research teams reviewed each candidate best paper, and (iii) the final selection of two best papers was conducted by the editorial board of the IMIA Yearbook. RESULTS: The two selected best papers demonstrate some of the promises and shortcomings of real-world data. CONCLUSION: Cancer informatics is a maturing subfield of biomedical informatics. Applications of informatics methods to real-world data are especially notable in 2021.

Real-World Treatment Patterns and Outcomes of Palbociclib Plus an Aromatase Inhibitor for Metastatic Breast Cancer: Flatiron Database Analysis.

INTRODUCTION: To describe real-world treatment patterns and effectiveness of first-line palbociclib plus an aromatase inhibitor (PAL+AI) and examine the association between PAL initial dose and effectiveness among patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic/advanced breast cancer (HR+/HER2- MBC) in routine clinical practice. PATIENTS AND METHODS: This retrospective analysis used Flatiron Health's database of electronic health records from >280 cancer clinics representing >2.4 million actively treated cancer patients in the United States. Women with HR+/HER2- MBC who received first-line PAL+AI were included. Real-world progression-free survival (rwPFS) was defined as the time from starting PAL+AI to death or disease progression. Real-world best tumor response (rwBTR) was assessed based on the treating clinician's assessment of radiologic evidence for change in disease burden. RESULTS: Of 813 eligible patients, median age was 65.0 years, and median follow-up was 21.0 months. PAL was initiated at 125 mg/d and 75/100 mg/d in 86.5% and 13.5% of patients, respectively. Median duration of PAL+AI was 16.3 months. 43.0% of patients discontinued PAL+ AI; 11.0% discontinued because of toxicity. Median time to subsequent therapy and chemotherapy was 24.6 and 36.6 months, respectively. Median rwPFS was 20.0 months, and best rwBTR rate was 51.9%. Patients starting PAL at 125 versus 75/100 mg/d had longer median rwPFS (27.8 vs. 18.6 months) and higher rwBTR rate (54.0% vs. 40.4%). CONCLUSION: These data demonstrate the benefit of PAL+AI in routine clinical practice and may support the initiation of palbociclib at the recommended dose of 125 mg/d for HR+/HER2- MBC. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT04176354, November 25, 2019.