Key Points Question Are patterns of medical aid in dying (MAID) use similar in Oregon and Washington? Findings In this cohort study of 3368 prescriptions for MAID in Oregon and Washington, most patients in both states were insured, non-Hispanic white individuals with some level of college education, with cancer being the most common underlying illness prompting MAID request. Annual percentage of patients per year who were prescribed medication and ingested it did not change in Oregon but increased over time in Washington, and in both states there were increasing deaths due to MAID per 1000 deaths over time. Meaning With the exception of use of prescribed medication, MAID patterns are similar in Oregon and Washington.

Background. The combination of everolimus (EVE) and exemestane (EXE) is approved for the treatment of metastatic hormone receptor-positive breast cancer (mHRBC) patients who progress on non-steroidal aromatase inhibitor (NSAI) therapy. However, none of the subjects enrolled in the trial that led to this approval (BOLERO-2) had previously received CDK4/6 inhibitors (CDK4/6is), which have since become a frontline standard of care for mHRBC. As such, the clinical benefit of EVE + EXE in patients who have previously received CDK4/6is remains unknown. Methods. Adult mHRBC patients at our institution who progressed on a NSAI + CDK4/6i or NSAI therapy alone and were treated with at least one cycle of EVE + EXE between 2012 and 2018 were analyzed. Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. Primary objectives were to compare progression-free survival (PFS) and overall survival (OS) between patients who received prior NSAI + CDK4/6i therapy versus a NSAI alone. Results. Among 43 patients, 17 had prior CDK4/6i exposure. With the exception of de novo metastatic disease, patient and disease characteristics were comparable across treatment cohorts. There was no significant difference in PFS (median 3.6 vs 4.2 months) or OS (median 15.6 vs 11.3 months) between patients who had received prior CDK4/6is and those who had not, respectively. Conclusion. Prior exposure to CDK4/6i therapy did not impact survival outcomes for mHRBC patients taking EVE + EXE. However, there was a trend towards improved OS in the CDK4/6i cohort that should be evaluated in larger cohorts. The Oncologist 2020;9999:• • Implications for Practice: The use of CDK4/6 inhibitors in combination with a non-steroidal aromatase inhibitor has become a standard frontline therapy in metastatic hormone receptor-positive breast cancer. An approved subsequent line of therapy is everolimus plus exemestane however the original data supporting this therapy predated prior of approval CDK4/6 inhibitors. As such, the clinical benefit of everolimus and exemestane in patients previously treated with a CDK4/6i was unknown. This retrospective cohort study offers real world data demonstrating prior CDK4/6 inhibitor exposure does not impact survival outcomes for everolimus plus exemestane.

As cells progress through carcinogenesis, the associated exponential expansion of genetic and molecular aberrations and resultant heterogeneity make therapeutic success increasingly unattainable. Therapeutic intervention at early stages of carcinogenesis that occurs within the primary organ and in the face of a lower burden of molecular aberrations, constitutes a basic tenet of cancer chemoprevention, and provides a situation that favors a greater degree of therapeutic efficacy compared with that of advanced cancer. A longstanding barrier to chemoprevention relates to the requirement for essentially no systemic toxicity, and the fact that when large numbers of people are treated, the emergence of systemic toxicity is almost universal. A rational means to address this in fact relates to a second basic tenet of the chemopreventive strategy: the focus of therapeutic intervention is to disrupt a process that is in essence localized to a single organ. Based upon this consideration, a strategy which is based upon local delivery of therapeutics to an at-risk organ will achieve therapeutic efficacy while avoiding systemic delivery and its associated toxicity. This article will review the rationale for undertaking such an approach, describe successful clinical achievements based on this strategy, describe ongoing efforts to expand the impact of this approach, and together will highlight the high impact that this approach has already had on the field as well as its extremely high potential for future impact. Cancer Prev Res; 10(1); 14-35. ©2016 AACR.

Background: Phase 3 studies of immune checkpoint inhibitors have not shown a survival benefit in prostate cancer, but some patients have a profound anticancer response. Patients and Methods: We evaluated the efficacy of the CTLA-4 targeted agent, ipilimumab, in metastatic prostate cancer patients who had an incomplete biochemical response to initial androgen deprivation therapy (ADT) alone. Ten patients were enrolled, each treated with ipilimumab 10 mg/kg (every 3 weeks for up to 4 doses) with maintenance ipilimumab every 12 weeks for non-progressing patients. The primary endpoint was proportion of patients with an undetectable PSA. The total sample size was 30 patients, but there was an interim analysis planned at 10 for futility. If none of the 10 patients achieved an undetectable PSA, the study would be halted. Results: The study was halted at the interim analysis as none of the 10 patients achieved the primary endpoint, but 30% of patients demonstrated a >50% reduction in PSA, with one patient achieving a >90% reduction in PSA. Peripheral blood mononuclear cells (PBMC) examined by mass cytometry showed that patients with clinical responses had an increase in effector memory T-cell subsets as well as an increase in T-cell expression of T-bet, suggesting induction of a Th1 response. Conclusions: This study provides further evidence that ipilimumab has activity in some patients with prostate cancer and provides further rationale for the development of future studies aimed at identifying a subset of patients with CPRC that are more likely to derive a benefit from treatment with ipilimumab.