The School of Breast Oncology® provides oncologists with a curriculum-based program that focuses exclusively on the clinical management of breast cancer, with a comprehensive review of data on the most important aspects of breast cancer biology, diagnostics, prevention, and treatment (including surgery, radiation therapy, and systemic therapy). The 13th Annual School of Breast Oncology®, was held November 5-7, 2015, in Atlanta, Georgia, and featured internationally recognized experts in breast cancer who discussed best practices and key advances for the treatment of patients across all stages of disease. This first of 3 PER Pulse™ Recaps from the School of Breast Oncology® focuses on the treatment of metastatic breast cancer (MBC), including subtype- and organ-specific considerations, as presented by William J. Gradishar, MD, FASCO, FACP; Ruth O'Regan, MD; Anne Moore, MD; Carey K. Anders, MD; and Catherine Van Poznak, MD.
The treatment algorithms for HER2+ and ER+ MBC have been evolving rapidly, with the introduction of several new agents. For patients with HER2+ MBC, pertuzumab plus trastuzumab and a taxane has become the preferred first-line therapy, based on the overall survival benefit demonstrated in the CLEOPATRA trial. Trastuzumab emtansine significantly improved overall survival compared with lapatinib plus capecitabine in taxane- and trastuzumab-pretreated patients, establishing it as the preferred second-line therapy. Dr. Gradishar reviewed the practical implications of these data in the clinic, later-line options, and controversies in the assessment of HER2 status.
Dr. O'Regan summarized evidence from recent trials investigating the CDK4/6 inhibitor palbociclib in combination with endocrine therapy for ER+/HER2– MBC, and how these clinical data impact treatment paradigms. The first-line phase II PALOMA-1 trial showed a significant 10 month improvement in progression-free survival (PFS) when palbociclib was added to letrozole, leading to FDA approval in February 2015. Similarly, in the phase III PALOMA-3 trial, the combination of palbociclib plus fulvestrant significantly increased median PFS from 3.8 months with fulvestrant alone to 9.2 months with the combination therapy in patients with disease progression on a prior endocrine therapy. Based on these results, the FDA approved palbociclib plus fulvestrant for this population in February 2016.
Cytotoxic chemotherapy remains a crucial component of treatment for triple-negative and endocrine-resistant ER+ MBC. Dr. Moore reviewed applicable ASCO guidelines, as well as the evidence supporting available cytotoxic agents. In addition, she addressed important clinical considerations such as selecting between sequential single agents versus combination treatment, determining duration of therapy, and managing patients with isolated, resectable metastases.
Dr. Van Poznak addressed the management of bone metastases, including scenarios dictating the use of bisphosphonates and the RANKL inhibitor denosumab, radiation, vertebroplasty, and kyphoplasty. Dr. Anders discussed the treatment of central nervous system metastases, including current options of radiation therapy or chemotherapy, as well as novel strategies under investigation.
The School of Breast Oncology® provides oncologists with a curriculum-based program focused exclusively on the clinical management of breast cancer, with a comprehensive review of data on the most important aspects of breast cancer biology, diagnostics, prevention, and treatment (including surgery, radiation therapy, and systemic therapy). The 13th Annual School of Breast Oncology®, was held November 5-7, 2015 in Atlanta, GA, and featured internationally recognized experts in breast cancer who discussed best practices and key advances for the treatment of patients across all stages of disease. This second of 3 PER Pulse™ Recaps from the School of Breast Oncology® focuses on the adjuvant treatment of early-stage breast cancer, as presented by Joyce O’Shaughnessy, MD, William J. Gradishar, MD, FASCO, FACP, and Edward H. Romond, MD.
Dr. O’Shaughnessy reviewed recent results from trials investigating the optimal treatment of premenopausal patients with hormone receptor-positive (HR+) early stage breast cancers, and how to integrate those results in the clinic. While 5 years of tamoxifen (with or without ovarian suppression) has long been the mainstay of treatment for this patient population, results from the SOFT and TEXT trials showed a significant improvement in breast cancer-free survival and distant recurrence-free survival with the combination of exemestane plus ovarian suppression compared with tamoxifen alone in premenopausal patients who previously received adjuvant chemotherapy, particularly in those under 35 years of age. Results from aTTom and ATLAS, as well as MA.17, provide support for longer durations of adjuvant endocrine therapy, and new ASCO guidelines provide direction on the management of pre- and peri-menopausal patients. Meanwhile, data from POEMS suggest inclusion of an LHRH agonist during adjuvant chemotherapy can help to preserve ovarian function, as well as improve survival outcomes.
Dr. Gradishar presented current adjuvant endocrine treatment standards for postmenopausal patients with HR+ breast cancer. Inclusion of an aromatase inhibitor (AI), either as upfront therapy or as part of a switch strategy integrating tamoxifen, remains standard and no substantial difference in efficacy or toxicity has been detected between the 3 available AIs. While numerous trials now show a benefit for extended adjuvant endocrine therapy, with either tamoxifen or tamoxifen followed by an AI, the optimal duration of AI therapy is still being investigated in clinical trials. Several molecular assays have also demonstrated preliminary utility in identifying those patients at the greatest risk of late recurrence, who may benefit most from extended treatment approaches. Ongoing trials are also evaluating the inclusion of targeted agents, such as mTOR and CDK4/6 inhibitors in adjuvant endocrine treatment strategies.
Adjuvant chemotherapy has long been standard for patients with node-positive and high risk node-negative early-stage breast cancers. Dr. O’Shaughnessy reviewed the evidence supporting current therapeutic options, and discussed how molecular assays that assess the risk of disease recurrence may be used to more precisely identify those patients most likely to benefit from adjuvant chemotherapy versus those who may be able to forego cytotoxic treatment, including those with T1a/b N0 cancers. Recent results from the CALOR trial providing support for an additional round of adjuvant chemotherapy for patients with locally recurrent disease who previously received and adjuvant chemotherapy regimen were also reviewed.
Dr. Romond summarized data from the pivotal trials that led to the inclusion of trastuzumab in adjuvant treatment regimens for HER2+ early-stage breast cancers, and discussed considerations, such as the optimal duration of HER2-targeted therapy, individualization of therapy for patients with cardiac risk factors, and options for patients with lower risk disease. In addition, he reviewed recent results from the phase III ExteNET trial that showed a significant improvement in invasive disease-free survival (iDFS), by extending treatment for 1 year with neratinib following completion of adjuvant chemotherapy plus trastuzumab (2-year iDFS 94% vs 92%; P = .009). Plans for an FDA submission, based on these results, are in progress.
The School of Breast Oncology® provides oncologists with a curriculum-based program focused exclusively on the clinical management of breast cancer, with a comprehensive review of data on the most important aspects of breast cancer biology, diagnostics, prevention, and treatment (including surgery, radiation therapy, and systemic therapy). The 13th Annual School of Breast Oncology® was held November 5-7, 2015 in Atlanta, GA, and featured internationally recognized experts in breast cancer who discussed best practices and key advances for the treatment of patients across all stages of disease. This third of 3 PER Pulse™ Recaps from the School of Breast Oncology® focuses on the management of side effects associated with breast cancer treatment, as presented by Frankie Ann Holmes, MD, FACP, Catherine Van Poznak, MD, and Charles Loprinzi, MD.
Dr. Holmes reviewed management strategies for chemotherapy-induced emesis, anemia, and myelosuppression. She discussed how to individualize anti-emetogenic strategies based on extrinsic factors (emetogenic profile of the chemotherapy regimen) and intrinsic factors (predisposing patient characteristics). She also summarized the mechanisms of action of different classes of anti-emetogenic agents, including receptor antagonists of 5HT3 and NK1, and steroids, as well as data supporting the recent approvals of the NK1 receptor antagonists netupitant (in combination with palonosetron) and rolapitant. She also reviewed guidelines for the use of erythrocyte stimulating agents for chemotherapy-induced anemia, and other management strategies including transfusions and iron supplementation. Finally, considerations for the use of myeloid growth factors to prevent febrile neutropenia were also discussed.
Dr. Van Poznak covered strategies to address several additional toxicities that can impact the quality of life of patients undergoing treatment for breast cancer. Fatigue is the most common side effect of cancer treatment, and affects over three-quarters of patients. Strategies that may help include physical activity, mind-body interventions like yoga or reiki, behavioral therapy, and self-monitoring; psychostimulants are undergoing clinical investigation. Approximately 75% of women report changes in cognitive function 2 years after receiving treatment, but causes are likely to be multifactorial. Effects typically subside over time, but interventions, such as structured cognitive rehabilitation programs, or pharmacologic interventions may also be helpful. Finally, several treatments, particularly hormonal therapies, can have a negative impact on bone mineral density which can increase risks for fragility fractures leading to significant morbidity and even mortality. Therapies that block the action of osteoclasts, such as bisphosphonates, and RANK Ligand inhibitors, have been shown to preserve BMD and decrease fracture risk.
Dr. Loprinzi rounded out the discussion with coverage of hot flashes and paclitaxel-induced neuropathy. Several antidepressants, such as paroxetine and venlafaxine were shown in a meta-analysis to reduce hot flashes compared with placebo. Gabapentin demonstrated similar efficacy compared with venlafaxine, but two-thirds of patients preferred venlafaxine in a randomized crossover trial. Other strategies, that have shown the ability to reduce the frequency or severity of hot flashes, include stellate ganglion block, hypnosis, and acupuncture. For paclitaxel-associated neuropathy, duloxetine may be of help, as well as gabapentanoids, tricyclic antidepressants, and topical baclofen/amitriptyline/ketamine gel.
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