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Chinese Medical Journal Nov 2023The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses.
METHODS
Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework.
RESULTS
This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively.
CONCLUSION
Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Afatinib; Lung Neoplasms; Bevacizumab; Bayes Theorem; Network Meta-Analysis; Protein Kinase Inhibitors; Pemetrexed; ErbB Receptors; Brain Neoplasms; Mutation
PubMed: 37160733
DOI: 10.1097/CM9.0000000000002468 -
JAMA Dermatology Aug 2023Chemotherapy-induced pseudocellulitis is an ill-defined term for a poorly understood phenomenon. Encompassing a myriad of cellulitis-mimicking oncologic adverse...
IMPORTANCE
Chemotherapy-induced pseudocellulitis is an ill-defined term for a poorly understood phenomenon. Encompassing a myriad of cellulitis-mimicking oncologic adverse cutaneous drug reactions (ACDRs), pseudocellulitis may be difficult to diagnosis, and the lack of treatment guidance may mean unnecessary antibiotic exposure and interruptions to oncologic care.
OBJECTIVES
To use case reports to characterize the various cellulitis-mimicking reactions caused by chemotherapeutic medications, to understand how these reactions affect patient care (ie, antibiotic exposure and interruptions to oncologic treatment), and to make recommendations for improved diagnosis and care of patients with chemotherapy-induced pseudocellulitis.
EVIDENCE REVIEW
A systematic review of case reports of patients with pseudocellulitis was performed. Reports were identified through database searches using PubMed and Embase, with subsequent reference searches. Included publications described at least 1 case of chemotherapy-induced ACDR and used the term pseudocellulitis or showed evidence of cellulitis mimicry. Cases of radiation recall dermatitis were excluded. Data were extracted from a total of 32 publications representing 81 patients diagnosed with pseudocellulitis.
FINDINGS
Of the 81 cases (median [range] age, 67 [36-80] years; 44 [54%] male patients), most were associated with gemcitabine use; pemetrexed use was reported less frequently. Only 39 were considered to be true chemotherapy-induced pseudocellulitis. These cases resembled infectious cellulitis and did not meet diagnostic criteria for any known diagnoses; therefore, these were described solely as pseudocellulitis. Of this group, 26 patients (67%) had been administered antibiotics before the correct diagnosis was made, and 14 patients (36%) experienced interruptions to their oncologic treatment plans.
CONCLUSIONS AND RELEVANCE
This systematic review found a variety of chemotherapy-induced ACDRs that mimic infectious cellulitis, including a group of reactions termed pseudocellulitis that do not meet criteria for other diagnoses. A more universally accepted definition and clinical research on chemotherapy-induced pseudocellulitis would allow for more accurate diagnosis, effective treatment, antibiotic stewardship, and continuation of oncologic treatment.
Topics: Humans; Male; Aged; Female; Deoxycytidine; Cellulitis; Antimetabolites, Antineoplastic; Gemcitabine; Drug-Related Side Effects and Adverse Reactions; Anti-Bacterial Agents
PubMed: 37379014
DOI: 10.1001/jamadermatol.2023.1735