Childersvilladsen6043

Luteinizing hormone-releasing hormone agonist (LHRH-A), goserelin, and antagonist, degarelix, are both indicated for the treatment of advanced prostate cancer (PCa); however, large comparative trials evaluating their efficacy and safety are lacking. In this review, we assessed the available evidence for both the drugs. Although degarelix achieves an early rapid decline in testosterone (T) and prostate-specific antigen (PSA) levels, median T and PSA levels, in addition to prostate volume and International Prostate Symptom Scores, become comparable with goserelin over the remaining treatment period. Degarelix causes no initial flare, therefore it is recommended in patients with spinal metastases or ureteric obstruction. Goserelin achieves lower PSA, improved time to progression, and better survival outcomes when administered adjunctively to radiotherapy compared with radiotherapy alone, with significant results even over long-term follow-up. The evidence supporting adjuvant degarelix use is limited. Goserelin has better injection site safety, single-step delivery, and an efficient administration schedule compared with degarelix, which has significantly higher injection site reactions and less efficient administration mechanism. There is conflicting evidence about the risk of cardiovascular disease (CVD), and caution is required when using LHRH-A in patients with preexisting CVD. There is considerable long-term evidence for goserelin in patients with advanced PCa, with degarelix being a more recent option. The available comparative evidence of goserelin versus degarelix has several inherent limitations related to study design, sample size, conduct, and statistical analyses, and hence warrants robust prospective trials and long-term follow-up.Androgen deprivation therapy (ADT) using gonadotropin-releasing hormone agonist (s) (GnRH-A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH-A. All GnRH-A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (≤50 ng/dL in a month and ≤20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ≤50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate-specific antigen suppression. CP21 In neoadjuvant setting, when only goserelin was used, the 10-year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10-year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10-year survival rate of 87%, and triptorelin had an 8-year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH-A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH-A. Goserelin appears to be the most convenient of all the GnRH-A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH-A for ADT in prostate cancer.Human epidermal growth factor receptor 2 (HER2)-negative subset is the most heterogeneous group of metastatic breast cancers (MBCs) as it includes both hormone receptor (HR)-positive and HR-negative breast cancer (or TNBC), which have different therapies and treatment challenges. Though endocrine therapy (ET) remains the treatment backbone in HR-positive HER2-negative cases, about 40% of the patients show intrinsic or acquired resistance to ET due to multiple mechanisms. Combining different therapies such as ET and other targeted therapies with or without chemotherapy fails to give continued benefit, unlike cyclin-dependent kinase (CDK) 4/6 inhibitors that have shown a great benefit. TNBC has conventionally been treated ineffectively with systemic chemotherapy. Recently, poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged for HER2-negative breast cancer (BC) patients, including TNBC. Olaparib and talazoparib have recently been approved in germline BRCA-mutated (gBRCAm) HER2-negative MBC. Additionally, ongoing trials of PARPi in combination with various therapies are expected to provide more and better treatment options for gBRCAm HER2-negative breast cancer.Standard therapy for advanced ovarian cancer (OC) consists of radical debulking cytoreductive surgery followed by adjuvant chemotherapy. An important risk factor for OC is genetic predisposition, with BRCA1 or BRCA2 mutations accounting for the majority of hereditary OC. Mutation in BRCA ultimately causes accumulation of genetic alterations because of the failure of cells to arrest and repair DNA damage or to undergo apoptosis, resulting in tumorigenesis. Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising approach for managing BRCA-associated cancers, especially high-grade OC and breast cancers. They lead to synthetic lethality in BRCA-mutated cells by stalling the replication forks in homologous recombination-deficient (HR) cells. Four PARP inhibitors (olaparib, niraparib, rucaparib, and talazoparib) are currently approved by the Food and Drug Administration for OC, breast, and pancreatic cancer indications and are being evaluated for other BRCA-associated cancers. Despite their clinical efficacy, cancer cells generally develop resistance to them through several mechanisms. Understanding these mechanisms is crucial for developing strategies to counter resistance and identify the basic mechanisms of DNA damage response. This review focuses on the mechanism of action of PARP inhibitors, understanding various causes of resistance, and building strategies to overcome PARP inhibitor resistance.Despite a better understanding of the pathophysiology and development of newer therapeutic options, cancer remains an area with several unmet needs. Although overall survival (OS) remains a gold standard endpoint for all cancer therapies, it poses challenges such as the requirement of a long-term follow-up, a higher number of patients, and a higher financial burden. Therefore, surrogate endpoints such as progression-free survival, time to progression, duration of response, and objective response rate are being investigated and used in oncology studies. Patient-related outcomes that measure the patient's overall health, quality of life, and satisfaction in the long term are crucial surrogate endpoints considered for drug approval. Surrogate endpoints shorten oncology clinical studies and accelerate the evaluation and implementation of newer therapies. Emerging surrogate endpoints such as biomarkers, immune-related response criteria, minimal residual disease, and pathological complete response are increasingly being considered in oncology trials. Validation of surrogate endpoints enables their substitution for OS and gain market approval. The selection of surrogate endpoints for an oncology trial depends on cancer type and stage, the purpose of treatment, and expected duration of survival for the relevant disease. With the advent of individualized approach and complex study designs, the field of oncology is currently undergoing a paradigm shift. The use of newer surrogate endpoints will aid in accelerating the drug development process, making patient care for oncology more accessible.Lung cancer is one of the deadliest cancers globally and accounts for most of the cancer-related deaths in India. Comprehensive data on lung cancer in India are lacking. This review aimed to discuss the epidemiological trends of lung cancers and driver mutations as well as the recent advancements in molecular diagnostics and therapeutic options primarily in non-small cell lung cancer (NSCLC) in India. Electronic databases, such as PubMed and Google Scholar, were searched to retrieve the relevant literature published in the past 5 years. As per the GLOBOCAN 2018 report, lung cancer was ranked the fourth leading cause of cancer (5.9% cases) in India, in all ages and sexes. Furthermore, 63,475 of all cancer-related deaths (8.1%) were attributed to lung cancer (cumulative risk 0.60), making it the third leading cause of cancer-related mortality. The common mutations that have been detected and targeted for treatment in lung cancer patients include EGFR, ALK, and PD-L1. In India, EGFR and ALK mutations are commonly reported, but not PD-L1 mutation. Molecular testing has gained importance as several biomarkers are being targeted to diagnose lung cancer patients. Surgery, radiotherapy, systemic chemotherapy, and personalized molecular-targeted therapy prolong the overall survival (OS) in patients with NSCLC. Although chemotherapy and molecular-targeted therapies have greatly improved the clinical outcomes, prolonged disease control could not be attained in most NSCLC patients. In this situation, immunotherapy seems to be potentially beneficial to obtain long-lasting disease control with minimal adverse events or safety concerns.Evidence from several studies has shown improved progression-free survival (PFS) with first- or second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) compared with chemotherapy for advanced NSCLC patients. But resistance to first or second-generation TKI therapies after 9 to 12 months of treatment initiation is a concern. Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFRm (epidermal growth factor receptor mutated) and EGFR T790M and has demonstrated efficacy in NSCLC central nervous system (CNS) metastases. Trials have reported significantly longer PFS and higher median duration of response with osimertinib compared with first-generation EGFR-TKIs (erlotinib, gefitinib) and chemotherapy, respectively. And relatively lower rates of discontinuation due to adverse events (AEs). Significant improvement in overall survival was also observed when used as first-line treatment. Because EGFR-mutated tumors are highly deuality of life. This review aims to determine the optimal sequence of administration of the EGFR-TKIs considering toxicity, quality of life, and survival outcomes among advanced NSCLC patients.EGFR-TKIs have changed the landscape of metastatic NSCLC treatment with a significant improvement in survival of EGFRm patients compared to wild-type EGFR. Even with the newer third generation EGFR TKIs like, Osimertinib, which has proven efficacy against the resistance mutation of EGFRm T790M, progression eventually occurs. There are limited treatment options for patients with metastatic EGFRm NSCLC with other acquired resistance. Therefore, novel therapeutic combination strategies are being researched to overcome potential resistance to EGFR-TKI-targeted therapy. The ICIs targeting the programmed cell death-1 pathway in patients with EGFRm NSCLC were greatly anticipated based on preclinical studies showing increased PD-L1 expression. In clinical settings, this increased expression did not translate into a survival benefit. Treatment with ICIs failed to positively affect EGFRm patients because of multiple reasons nonsynonymous tumor mutational burden, lower PD-L1 expression in tumors, and cancer cells utilizing alternate immune escape mechanisms.