ABSTRACT
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.
Subject(s)
Antineoplastic Agents, Immunological , Autoimmune Diseases , Neoplasms , Adrenal Cortex Hormones/therapeutic use , Adult , Antineoplastic Agents, Immunological/adverse effects , Autoimmune Diseases/complications , Autoimmune Diseases/drug therapy , Humans , Neoplasms/drug therapy , Nivolumab/adverse effects , Programmed Cell Death 1 Receptor , Prospective Studies , Retrospective StudiesABSTRACT
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.
ABSTRACT
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.
Subject(s)
Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Trastuzumab/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Administration Schedule , Duration of Therapy , Female , Humans , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Randomized Controlled Trials as Topic , Receptor, ErbB-2/antagonists & inhibitors , Trastuzumab/adverse effects , Treatment OutcomeABSTRACT
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.
