Prior Treatment Time Affects Survival Outcomes in Metastatic Breast Cancer

PURPOSE Sequential drug treatments in metastatic breast cancer (MBC) are disparate. Clinical trial data includes limited reporting of treatment context, primarily including the number of prior therapies. This study evaluates the relationship between prior treatment time, prior lines of treatment, and survival using a novel visualization technique coupled with statistical analyses. PATIENTS AND METHODS This retrospective cohort study used a nationwide, de-identified electronic health record–derived database to identify women with hormone receptor–positive, human epidermal growth factor receptor 2–negative MBC diagnosed in 2014 who subsequently received paclitaxel. Images were created, with individual patients represented on the y-axis and time, on the x-axis. Specific treatments were represented by colored bars, with Kaplan-Meier curves overlaying the image. Separate images assessed progression-free survival and overall survival (OS). Hazard ratios (HRs) and 95% CIs from Cox proportional hazards models evaluated the association between prior treatment time and OS. RESULTS Of 234 patients, median survival from first paclitaxel administration was 20 months (interquartile range, 8-53 months). An inverse relationship was observed between OS after paclitaxel and timing of administration. In adjusted models, each year on treatment prior to paclitaxel was associated with a 16% increased hazard of death after paclitaxel (HR, 1.16; 95% CI, 1.05 to 1.29). CONCLUSION OS after a specific treatment is dependent on when a drug is given in the disease context, highlighting the potential for an overall OS benefit to be observed on the basis of treatment timing. Prior time on treatment should be considered as a stratifying factor in randomized trials and a confounding factor when examining survival in observational data.

[1]  M. Burkard,et al.  Visualization of Sequential Treatments in Metastatic Breast Cancer. , 2020, JCO clinical cancer informatics.

[2]  P. Neven,et al.  The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2 , 2019, JAMA oncology.

[3]  Sandra D Griffith,et al.  Characterizing the Feasibility and Performance of Real-World Tumor Progression End Points and Their Association With Overall Survival in a Large Advanced Non–Small-Cell Lung Cancer Data Set , 2019, JCO clinical cancer informatics.

[4]  A. Abernethy,et al.  Real‐world progression, treatment, and survival outcomes during rapid adoption of immunotherapy for advanced non–small cell lung cancer , 2019, Cancer.

[5]  M. Aapro,et al.  Randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel in estrogen receptor-positive, HER2-negative patients with advanced breast cancer (NorBreast-231 trial). , 2019, Breast.

[6]  H. Rugo,et al.  Alpelisib for PIK3CA‐Mutated, Hormone Receptor–Positive Advanced Breast Cancer , 2019, The New England journal of medicine.

[7]  S. Khozin,et al.  Generating Real-World Tumor Burden Endpoints from Electronic Health Record Data: Comparison of RECIST, Radiology-Anchored, and Clinician-Anchored Approaches for Abstracting Real-World Progression in Non-Small Cell Lung Cancer , 2019, bioRxiv.

[8]  S. Loi,et al.  Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. , 2018, European journal of cancer.

[9]  S. Bhatia,et al.  Concordance with NCCN treatment guidelines: Relations with health care utilization, cost, and mortality in breast cancer patients with secondary metastasis , 2018, Cancer.

[10]  S. Bhatia,et al.  Impact of Nonconcordance With NCCN Guidelines on Resource Utilization, Cost, and Mortality in De Novo Metastatic Breast Cancer. , 2018, Journal of the National Comprehensive Cancer Network : JNCCN.

[11]  P. Fasching,et al.  Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Abernethy,et al.  Development and Validation of a High‐Quality Composite Real‐World Mortality Endpoint , 2018, Health services research.

[13]  M. Goetz,et al.  MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  R. Porcher,et al.  Differences in Treatment Effect Size Between Overall Survival and Progression-Free Survival in Immunotherapy Trials: A Meta-Epidemiologic Study of Trials With Results Posted at ClinicalTrials.gov. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  A. Deaton,et al.  Understanding and Misunderstanding Randomized Controlled Trials , 2016, Social science & medicine.

[16]  V. Kaklamani Clinical Implications of the Progression-Free Survival Endpoint for Treatment of Hormone Receptor-Positive Advanced Breast Cancer. , 2016, The oncologist.

[17]  Amy P Abernethy,et al.  Opportunities and challenges in leveraging electronic health record data in oncology. , 2016, Future oncology.

[18]  J. Signorovitch,et al.  Real-world patterns of endocrine therapy for metastatic hormone-receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2−) breast cancer patients in the United States: 2002–2012 , 2014, Current medical research and opinion.

[19]  M. Bonafede,et al.  Patterns of treatment, healthcare utilization and costs by lines of therapy in metastatic breast cancer in a large insured US population. , 2013, Journal of comparative effectiveness research.

[20]  M. Buyse,et al.  Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  E. Perez,et al.  Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. , 2007, The New England journal of medicine.

[22]  S. Johnston,et al.  Factors determining outcome after third line chemotherapy for metastatic breast cancer. , 2007, Breast.

[23]  B. Overmoyer,et al.  Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  J. Klijn,et al.  Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Edward J. Mulrow,et al.  The Visual Display of Quantitative Information , 1985, Technometrics.

[26]  S. Loi,et al.  Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. , 2017, New England Journal of Medicine.

[27]  Xin Huang,et al.  The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. , 2015, The Lancet. Oncology.