Improving palbociclib adherence among women with metastatic breast cancer using a CONnected CUstomized Treatment Platform: A pilot study.

OBJECTIVE: To pilot test a mobile health intervention using a CONnected CUstomized Treatment Platform that integrates a connected electronic adherence monitoring smartbox and an early warning system of non-adherence with bidirectional automated texting feature and provider alerts. METHODS: In total, 29 adult women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer and a prescription for palbociclib were asked to complete a survey and participate in a CONnected CUstomized Treatment Platform intervention, including use of a smartbox for real-time adherence monitoring, which triggered text message reminders for any missed or extra dose, and referrals to (a) participant's oncology provider after three missed doses or an episode of over-adherence, or (b) a financial navigation program for any cost-related missed dose. Use of smartbox, number of referrals, palbociclib adherence, CONnected CUstomized Treatment Platform usability measured by System Usability Scale, and changes in symptom burden and quality of life were assessed. RESULTS: Mean age was 57.6 and 69% were white. The smartbox was used by 72.4% of participants, with palbociclib adherence rate of 95.8%±7.6%. One participant was referred to oncology provider due to missed doses and one was referred to financial navigation. At baseline, 33.3% reported at least one adherence barrier including inconvenience to get prescription filled, forgetfulness, cost, and side effects. There were no changes in self-reported adherence, symptom burden or quality of life over 3 months. CONnected CUstomized Treatment Platform usability score was 61.9 ± 14.2. CONCLUSION: The CONnected CUstomized Treatment Platform interventions is feasible, resulting in a high palbociclib adherence rate without any decline in overtime. Future efforts should focus on improving usability.

A Safety Analysis of Programmed Death 1 Pathway Inhibitors in Patients With Solid Tumor Malignancies and Preexisting Autoimmune Disease.

OBJECTIVE: The aim of this study was to characterize the safety of programmed death 1 inhibitors in patients with preexisting autoimmune disease. METHODS: A medical records review study was conducted on adults with solid tumor malignancies who received ≥1 dose of pembrolizumab or nivolumab at Emory Healthcare from September 4, 2014 until December 31, 2019. All autoimmune patients were included (n = 77), whereas the nonautoimmune patients were randomized and the first 156 patients were included in a 2:1 ratio to autoimmune patients. The primary objective was the comparison of incidence of immune-related adverse events (irAEs) between patients with preexisting autoimmune disease and those without. Secondary objectives included irAE characterization, irAE treatment, and survival analyses. RESULTS: Preexisting autoimmune disease was controlled in all of the autoimmune patients before immunotherapy initiation. The rate of irAE was 32.7% in the nonautoimmune group and 42.9% in the autoimmune group (odds ratio, 0.65; 95% confidence interval, 0.37-1.14; p = 0.130). In the patient population diagnosed with a rheumatologic autoimmune disease, 23.81% of irAEs were considered to be a flare of their preexisting autoimmune disease. Less patients in the autoimmune group experienced a grade ≥3 irAE (21.21% vs 37.25%, p = 0.379) and received systemic corticosteroids (54.55% vs 67.35%, p = 0.241) for the treatment of the irAE. CONCLUSIONS: These results suggest that pembrolizumab and nivolumab can be safely administered in patients with controlled preexisting autoimmune diseases without a significant increase in irAE compared with patients without autoimmune diseases. Inclusion of patients with preexisting autoimmune diseases in prospective clinical trials is warranted.

Optimizing the Duration of Trastuzumab: A Fresh Perspective.

Prior to the introduction of trastuzumab, the first targeted anti-HER2 agent, in 1998, patients diagnosed with HER2-positive breast cancer felt like they were being handed a death sentence. Despite treatment with aggressive chemotherapy, their tumors recurred faster, more often spread to brain and liver, and were associated with higher rates of death than HER2-negative tumors. HER2-positive breast cancer was also more prevalent in younger patients, making the diagnosis even more devastating. However, in the 1980s, cancer researcher Axel Ullrich, PhD, and oncologist Dennis Slamon, MD, PhD, recognized that HER2 could be targeted by a small molecule that binds to the receptor on the cell surface and blocks the signal telling the cell to divide. This small molecule was called trastuzumab, and it eventually completely changed how HER2-positive breast cancer was treated.

Leveraging Mobile Health to Improve Capecitabine Adherence Among Women With Breast Cancer: A Pilot Randomized Controlled Trial.

PURPOSE: Oral capecitabine improves convenience compared to intravenous therapies but presents monitoring challenges. We conducted a randomized pilot trial to evaluate a mobile health intervention to remotely monitor capecitabine adherence and patient-reported outcomes (PROs) among women with breast cancer. METHODS: Patients with breast cancer prescribed capecitabine, an oral chemotherapy with a complex, cyclical regimen, were randomly assigned to enhanced usual care (EUC) or PRO arm. Participants were asked to use a smart pill bottle to measure adherence (timing and dose) and complete baseline and 90-day follow-up surveys. PRO participants received text messages for missed or incorrect doses and weekly text-based symptom assessments, and their oncologists received alerts for severe symptoms or missed doses. We compared nonadherence (<80%) and changes from enrollment to follow-up on reported physical and mental health quality-of-life scores and number of severe symptoms by study arm. RESULTS: Overall, 32 women were randomly assigned (17 EUC and 15 PRO): 28 (87.5%) received the intervention and 24 (78.1%) completed the follow-up survey. Among participants who received the intervention, PRO participants responded to 83.3% of symptom questions; 7.7% of PRO participants were nonadherent compared with 40.0% of EUC participants (P = .049). Among those who completed the follow-up survey, 12.5% of PRO participants had reductions in their mental health composite scores compared with 69.2% of EUC participants (P = .011); 10% of PRO participants had more severe symptoms at follow-up compared with 57.1% of EUC participants (P = .019). CONCLUSION: A mobile health intervention using text message reminders and symptom assessments improved medication adherence and mental health quality-of-life scores and lowered symptom burden of patients with breast cancer prescribed capecitabine. Future work should evaluate the longer-term impacts of this intervention.

Ribociclib and Abemaciclib: CDK4/6 Inhibitors for the Treatment of Hormone Receptor-Positive Metastatic Breast Cancer.

The treatment landscape of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer has been modernized by the identification of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Because the majority of HR+ breast cancers will develop resistance to endocrine therapies (tamoxifen and aromatase inhibitors), newer treatment options are necessary to restore endocrine sensitivity and prolong survival. Ribociclib and abemaciclib are two of three CDK4/6 inhibitors currently approved for first- and second-line treatment of HR+/HER2- metastatic breast cancer. Data from large, phase III clinical trials have demonstrated an improvement in both progression-free and overall survival with the addition of ribociclib or abemaciclib to endocrine-based therapy, establishing a new frontline standard of care. Treatment with ribociclib and abemaciclib provide a convenient oral treatment option that is both efficacious and well tolerated.

Olaparib: A Novel Therapy for Metastatic Breast Cancer in Patients With a BRCA1/2 Mutation.

Breast cancer is the most frequently diagnosed cancer in women globally. Genetic mutations can increase the risk of developing breast cancer. Inherited germline mutations in BRCA1 and BRCA2 tumor suppressor genes (gBRCAm) account for 5% to 10% of breast cancer cases. The recent approval of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in HER2-negative, metastatic breast cancer provides an additional treatment option for patients with a gBRCAm. Inhibition of PARP results in the trapping of the PARP-DNA complex at replication forks, causing single-strand breaks to become double-strand breaks (DSBs). PARP trapping and the accumulation of DSBs ultimately leads to cell apoptosis. Cells deficient in BRCA1/2 are particularly sensitive to the effects of PARP inhibition, as cells lacking these functional proteins are unable to repair DSBs, resulting in synthetic lethality. The phase III OlympiAD trial showed a progression-free survival benefit but no overall survival benefit, leading to the US Food and Drug Administration approval of olaparib. The purpose of this article is to describe current data regarding the use of olaparib in metastatic breast cancer, its role in the treatment of patients with a gBRCAm, and the clinical implications of its approval for oncology advanced practitioners.