Impact of a specialty pharmacy case management service on adherence in patients receiving oral antineoplastic agents.

Background Patients receiving treatment with oral antineoplastic agents encounter several barriers to adherence, which may include high medication costs, limited access to specialty medications, severe adverse effects, complex medication regimens, and special handling precautions. Medication nonadherence not only reduces the efficacy of drug therapy but also has the potential to increase healthcare expenditures due to disease-related hospitalizations. Although several previous studies have examined patient adherence to oral antineoplastic agents, few have examined the impact of a specialty pharmacy case management service. Methods Patient adherence to oral antineoplastic agents was evaluated through a retrospective analysis of pharmacy claims data and medical chart reviews. The medication possession ratio (MPR) was used to quantitatively measure adherence during two 6-month intervals, prior to and following the implementation of a case management service. Patients with an MPR greater than or equal to 0.8 were categorized as adherent, while those with an MPR less than 0.8 were categorized as non-adherent. Results During the first 6-month interval prior to implementation of the case management service (n = 40), a cumulative average MPR of 0.922 was observed. Following implementation of the case management service (n = 56), a non-statistically significant (p = 0.199) increase in MPR to 0.941 was identified. For patients categorized as non-adherent, a nonstatistically significant (p = 0.214) decrease from 15% to 7% was identified following the introduction of the case management service. Conclusion Study results from this retrospective review indicate that case management services provided through an outpatient specialty pharmacy may have the potential to improve patient adherence to oral antineoplastic agents.

Down's Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship.

Down's syndrome (DS), the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21). Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H., The Lancet Oncology, 2001). A study conducted in the United States found only one death when 11.65 were expected (Scholl T et al., Dev Med Child Neurol. 1982). A recent study examined mammogram reports of women with DS treated in the largest medical facility specifically serving adults with DS in the United States. It was found that only 0.7% women with DS had been diagnosed with breast cancers (Chicoine B et al., Intellect Dev Disabil. 2015). Here we describe a case of breast cancer in a 25-year-old patient with DS. The disease was presented as lymph node positive carcinoma with alterations of tumor suppressor genes characteristic to the triple negative breast cancer subtype. Comprehensive Genomic Profiling (CGP) revealed a wild-type status for BRCA1. The CGP report showed a frameshift mutation, A359fs*10 of the tumor suppressor gene INPP4B and another frameshift mutation, R282fs*63 of tumor suppressor gene TP53 in the tumor biopsy as characteristically found in triple-negative breast cancers. The VUS (Variance of Unknown Significance) alteration(s) were identified in ASXL1 (L1395V), NTRK1 (G18E), DDR2 (I159T), RUNX1 (amplification), ERG (amplification), SOX2 (T26A), FAM123B (G1031D), and HNF1A (A301T). Bonafide cancer-related genes of chromosome 21 amplified in the patient's tumor are RUNX1 and ERG genes. After the completion of the radiation, the patient was placed on everolimus which was based on the result of her CGP report. Thus, post-mastectomy radiation therapy was completed with a recommendation for everolimus for one year. During the time of writing of this report, no metastatic lesions were identified. The patient currently has no evidence of disease.

Genomic Considerations in the Treatment of Thyroid Carcinoma.

Highlighting genomically driven targeted therapies to improve outcomes in advanced thyroid carcinoma.

A phase 1 evaluation of the safety and tolerability of niraparib in combination with everolimus in advanced ovarian and breast cancers.

OBJECTIVES: Phase 1 trial to determine the safety and tolerability of everolimus and niraparib in patients with advanced ovarian and breast malignancies. RESULTS: Fourteen heavily pretreated patients were enrolled (12 high-grade serous ovarian cancer, 1 clear cell ovarian cancer, and 1 triple negative breast cancer). All patients were PARP naïve and received comprehensive genomic profiling prior to enrollment. Two DLTs were experienced in cohort 2 (niraparib 200 mg daily and everolimus 5 mg 3 days per week) with one patient experiencing prolonged thrombocytopenia and the other experiencing severe hypertension. Four additional patients were enrolled after dose de-escalation with one patient again experiencing severe hypertension leading to conclusion of the study. The most frequent grade 3 or greater adverse events were thrombocytopenia, hypertension, anemia, fatigue, neutropenia, and elevated alkaline phosphatase. Two patients had a PR and five patients had SD. ORR was 18% and the CBR was 45% in 11 evaluable patients. Median PFS was 6 months, and median OS is approximately 18 months with three patients still alive at the data cutoff. CONCLUSIONS: The combination of everolimus and niraparib demonstrated significant toxicity at lower doses and is not feasible due to rapid onset and severe hypertension. This limitation possibly blunted the efficacy of the combination as PFS was modest, but OS was surprisingly robust due to three patients with ovarian cancer remaining alive with platinum refractory disease. Further investigation of multiagent blockade of the PI3K pathway combined with PARP is warranted.

Case report: 16-yr life history and genomic evolution of an ER+ HER2- breast cancer.

Metastatic breast cancer is one of the leading causes of cancer-related death in women. Limited studies have been done on the genomic evolution between primary and metastatic breast cancer. We reconstructed the genomic evolution through the 16-yr history of an ER+ HER2- breast cancer patient to investigate molecular mechanisms of disease relapse and treatment resistance after long-term exposure to hormonal therapy. Genomic and transcriptome profiling was performed on primary breast tumor (2002), initial recurrence (2012), and liver metastasis (2015) samples. Cell-free DNA analysis was performed at 11 time points (2015-2017). Mutational analysis revealed a low mutational burden in the primary tumor that doubled at the time of progression, with driver mutations in PI3K-Akt and RAS-RAF signaling pathways. Phylogenetic analysis showed an early branching off between primary tumor and metastasis. Liquid biopsies, although initially negative, started to detect an ESR1 E380Q mutation in 2016 with increasing allele frequency until the end of 2017. Transcriptome analysis revealed 721 (193 up, 528 down) genes to be differentially expressed between primary tumor and first relapse. The most significantly down-regulated genes were TFF1 and PGR, indicating resistance to aromatase inhibitor (AI) therapy. The most up-regulated genes included PTHLH, S100P, and SOX2, promoting tumor growth and metastasis. This phylogenetic reconstruction of the life history of a single patient's cancer as well as monitoring tumor progression through liquid biopsies allowed for uncovering the molecular mechanisms leading to initial relapse, metastatic spread, and treatment resistance.

Utilizing Tumor and Plasma Liquid Biopsy in Treatment Decision Making for an Estrogen Receptor-Positive Advanced Breast Cancer Patient.

Breast cancer affects 12% of females in the United States and is the leading cause of cancer death in the female population. Personalized therapy is being used in clinical practice to treat breast cancer based on tumor molecular profiling, which can be obtained from tissue biopsy or plasma liquid biopsy as circulating tumor deoxyribonucleic acid (ctDNA). The available ctDNA tests provide a non-invasive way to monitor the cancer genome in a real-time manner. In this case report, a 38-year-old female with recurrent estrogen receptor (ER) positive breast cancer is treated with letrozole, everolimus, and palbociclib. The drugs target the hormonal signaling pathway, phosphoinositide 3-kinase (PI3K)-RAC-alpha serine/threonine-protein kinase (AKT) pathway, and cyclin D1 (CCND1)-CDK4/6 pathway, based on the patient's estrogen-receptor-positive (ER+) disease and phosphatidylinositol -4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, as well as PIK3CA and CCND1 amplification. After 11 months of treatment, retinoblastoma protein transcriptional corepressor 1 (RB1) mutation was caught in ctDNA, which suggests an acquired resistance to palbociclib. Pazopanib was then used instead of palbociclib, targeting the fibroblast growth factor 3/4/19 (FGF3/4/19) amplification that was initially observed in her molecular profiling. Trametinib was also suggested recently due to the increasing allele frequency of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in ctDNA, following the treatment of letrozole + everolimus + pazopanib. The patient has no evidence of disease after five months of treatment initiation and has remained disease-free for over 16 months. In conclusion, the analysis of ctDNA is an effective way to monitor the real-time changes in a patient's tumor genome, which is a great supplement to the molecular profile from the tissue biopsy. The combination of these two tests provides an efficient strategy to make more informed treatment decisions, which greatly adapt along disease development.