Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation.

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center. Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation. Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation. Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies

Effect of neoadjuvant chemotherapy regimen on relapse-free survival among patients with breast cancer achieving a pathologic complete response: an early step in the de-escalation of neoadjuvant chemotherapy

Abstract Background Patients with breast cancer who have a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize that once pCR has been achieved, there is no difference in subsequent postsurgical recurrence-free survival (RFS), whichever NACT regimen is used. Methods Data from patients with breast cancer who achieved pCR after NACT between 1996 and 2011 were reviewed. RFS was estimated by the Kaplan-Meier method, and differences between groups were assessed using log-rank testing. Cox proportional hazards regression analysis adjusted for age, menopausal status, stage, grade, tumor subtype, and adjuvant endocrine HER2-targeted radiation treatment. Results Among 721 patients who achieved pCR after NACT, 157 (21.8%) were hormone receptor-positive (HR), 310 (43.3%) were HER2-amplified, and 236 (32.7%) were triple-negative; 292 (40.5%) were stage IIA, 153 (21.2%) were stage IIB, 78 (10.8%) were stage IIIA, 66 (9.2%) were stage IIIB, and 132 (18.3%) were stage IIIC. Most patients (367 [50.9%]) had been treated with adriamycin-based chemotherapy plus taxane (A + T), 56 (7.8%) without taxane (A no T), 227 (31.5%) with HER2-targeted therapy, and 71 (9.8%) provider choice. Median follow-up was 7.1 years. Adjuvant chemotherapy was employed in 196 (27%) patients, adjuvant endocrine in 261 (36%), and adjuvant radiation in the majority (559 [77.5%]). There was no statistically significant difference in RFS by NACT group. Adjusted RFS hazard ratios, comparing each treatment with the reference group A + T, were 1.25 (95% CI 0.47–3.35) for A no T, 0.90 (95% CI 0.37–2.20) for HER2-targeted therapy, and 1.28 (95% CI 0.55–2.98) for provider choice. Conclusions These data suggest that postsurgical RFS is not significantly influenced by the choice of NACT or cancer subtype among patients achieving pCR

Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation.

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center. Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation. Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation. Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies