Efficacy and Safety of RET-Specific Kinase Inhibitors in RET-Altered Cancers: A Systematic Review.

RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.

Efficacy and Safety of Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma: A Systematic Review of Clinical Trials.

Renal cell carcinoma (RCC) is the most common kidney cancer in adults (approximately 90%), and clear cell RCC (ccRCC) is the most frequent histologic subtype (approximately 75%). We reviewed the safety and efficacy of checkpoint inhibitors (CPIs) in ccRCC, identifying 5927 articles in PubMed, Embase, Cochrane, and Web of Science. Ten randomized control (N = 7765) and 10 non-randomized (N = 572) studies were included. Overall, 4819 patients treated with CPI combinations were compared with everolimus, sunitinib, or placebo. Overall response rates (ORR) were 9-25% with nivolumab (niv), 42% with niv + ipilimumab (ipi), 55.7% with niv + cabozantinib, 56% with niv + tivozanib vs. 5% with everolimus. ORR was 51.5-58% with avelumab + axitinib vs. 25.5% with sunitinib. ORR was 59.3-73% with pembrolizumab + tyrosine kinase inhibitor vs. 25.7% with sunitinib. ORR was 32-36% with atezolizumab + bevacizumab vs. 29-33% with sunitinib. In patients with PD-L1+ve and -ve ccRCC, niv, atezolizumab, ipi, and pembrolizumab were safe and effective alone and when combined with cabozantinib, tivozanib, axitinib, levantinib, and pegilodecakin. Atezolizumab + bevacizumab was safe and effective in ccRCC with high PD-L1 expression. Pembrolizumab was safe and effective in preventing recurrence in ccRCC patients with nephrectomy. Additional randomized, double-blind, multicenter clinical trials are needed to confirm these results.

Efficacy and Safety of Oral GnRh Antagonists in Patients With Uterine Fibroids: A Systematic Review.

OBJECTIVE: This review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids. DATA SOURCES: A literature search was performed on PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov using the MeSH and Emtree terms "leiomyoma" and "gonadotropin-releasing hormone." STUDY SELECTION: All clinical trials that provided efficacy and safety data in clinical terms (i.e., reduction in menstrual bleeding and discomfort, changes in the size of leiomyoma and uterine volume, etc.) were included. We excluded all preclinical studies, case reports, meta-analyses, review articles, and clinical studies irrelevant to the study question. DATA EXTRACTION AND SYNTHESIS: Two authors extracted data from 9 clinical studies. The extracted data included the study's characteristics, participants' baseline characteristics, treatment drugs, efficacy measures, and toxicity. CONCLUSION: Among oral GnRH antagonists, relugolix, elagolix, and linzagolix were safe in patients with uterine fibroids. These drugs, alone and in combination with E2/NETA (estradiol/norethindrone acetate), showed significantly better efficacy than placebo in improving bleeding, discomfort, uterine/leiomyoma sizes, and quality of life in premenopausal patients with symptomatic uterine fibroids. However, more randomized, double-blind, multicentre clinical trials are needed to confirm these results and to see long-term benefits.

Efficacy and toxicity of surufatinib in neuroendocrine tumors: A systematic review and meta-analysis.

The incidence and prevalence of neuroendocrine neoplasms (NENs) has increased in the US in recent decades. These are well-vascularized tumors, but no antiangiogenic drug has been approved for treatment of extra-pancreatic NENs. The aim is to assess efficacy and safety of surufatinib in pancreatic and extra-pancreatic NETs. We searched PubMed, Embase, Cochrane Library, Web of Science and Clinicaltrials.gov. Clinical trials and observational studies that provided safety and efficacy data in clinical terms were included. Characteristics of the study, baseline characteristics of participants, treatment drugs, measures of efficacy, and toxicity (≥grade 3 adverse effects) were extracted. The meta-analysis was performed using the "R" programming language. Risk ratio (RR) of objective response (OR)/partial response (PR) was 8.55 (95% CI: 1.68-43.66, I2  = 0) in favor of surufatinib. The hazard ratio (HR) of progression-free survival (PFS) was 0.48 (95% CI: 0.25-0.92, I2  = 77%) in favor of surufatinib. The risk of ≥grade 3 adverse effects: diarrhea, hypertension, hypertriglyceridemia, proteinuria, and vomiting were high with the use of surufatinib. Quality of life (QoL) was similar in surufatinib and placebo groups except for the diarrhea that was high with surufatinib. Lack of randomized clinical trials in non-Chinese population. Surufatinib is well tolerated and is more effective than placebo in both pancreatic and extra-pancreatic NETs. More multicenter randomized, double-blinded clinical trials are needed to confirm these results.

Current Status of Monoclonal Antibodies-Based Therapies in Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials.

Background Multiple patients with prostate cancer become resistant to castration therapies, which is termed castration-resistant prostate cancer (CRPC). Purpose The purpose of this review is to assess the status of efficacy (≥50% decline in prostate-specific antigen (PSA), progression-free survival (PFS), and overall survival (OS)) and safety (grade 3-4 adverse effects) of monoclonal antibodies in CRPC. Data source We searched databases including PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov. Results Hazard ratios of PFS and OS were 0.77 (95% CI = 0.69-0.87, I2 = 53%) and 0.98 (95% CI = 0.86-1.11, I2 = 40%), respectively, in the favor of monoclonal antibodies as compared to placebo. Risk ratio (RR) of >50% decline in PSA was 1.99 (95% CI = 0.97-4.08, I2 = 53%) in favor of monoclonal antibodies. Pooled incidence of >50% decline in PSA levels was 15% (95% CI = 0.1-0.23, I2 = 83%), 29% (95% CI = 0.14-0.51, I2 = 93%), 63% (95% CI = 0.49-0.76, I2 = 77%), and 88% (95% CI = 0.81-0.93, I2 = 0%) in single, two, three, and four-drug regimens, respectively. Conclusion Monoclonal antibodies are well tolerated and showed better PFS as compared to placebo. However, OS was only improved with ipilimumab. Denosumab delayed skeletal-related adverse events as compared to zoledronic acid. More multicenter double-blind clinical trials may be needed to confirm these results.