Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer: A systematic review and meta-analysis of clinical trials.

Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61-0.84, I2 = 71%) and 0.73 (95% CI = 0.64-0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51-0.61) and 0.59 (95% CI = 0.54-0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54-0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22-0.37) and 0.55 (95%CI = 0.36-0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.

A Clinical Overview of Anorexia Nervosa and Overcoming Treatment Resistance.

Anorexia nervosa (AN) is a type of eating disorder that has been increasing in incidence and has been encountered more commonly by physicians in their daily practice. Both environmental and genetic risk factors paired along with a more susceptible neurobiology are at play in the emerging resistance to treatment in AN. Preoccupations with intense fear of weight gain, dietary restrictions, excessive exercise, and how the individual is perceived by society mixed with underlying psychopathology all further add to the issue. Many patients who fall into this cycle of obsessive and restrictive patterns refuse to get treatment. As clinicians, it is essential we recognize the early signs of both eating disorders during the initial primary care appointments. To review the literature on the etiology of AN, possible misdiagnosis leading to inappropriate management of this condition, and understand the treatment-resistant AN and its management. Additionally, it will explore possible reasons that contribute to the resistance to treatment, the underlying psychopathology of anorexics, its genetic predisposition, psychiatric comorbidities, identification of the early signs and symptoms, and timely prevention. Early recognition by a physician includes a thorough history and physical examination, pertinent laboratory, and electrolyte studies, and identifying comorbid psychiatric conditions. The treatment of AN is intricate and requires a holistic approach. Treatment includes multiple modalities such as nutritional rehabilitation and psychosocial and pharmacological therapies. An interdisciplinary team of medical professionals for managing chronic AN is recommended.