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BMC Cancer Feb 2024The partitioned survival model (PSM) and the state transition model (STM) are widely used in cost-effectiveness analyses of anticancer drugs. Using different modeling...
Comparison of partitioned survival modeling with state transition modeling approaches with or without consideration of brain metastasis: a case study of Osimertinib versus pemetrexed-platinum.
BACKGROUND
The partitioned survival model (PSM) and the state transition model (STM) are widely used in cost-effectiveness analyses of anticancer drugs. Using different modeling approaches with or without consideration of brain metastasis, we compared the quality-adjusted life-year (QALY) estimates of Osimertinib and pemetrexed-platinum in advanced non-small cell lung cancer with epidermal growth factor receptor mutations.
METHODS
We constructed three economic models using parametric curves fitted to patient-level data from the National Health Insurance Review and Assessment claims database from 2009 to 2020. PSM and 3-health state transition model (3-STM) consist of three health states: progression-free, post-progression, and death. The 5-health state transition model (5-STM) has two additional health states (brain metastasis with continuing initial therapy, and with subsequent therapy). Time-dependent transition probabilities were calculated in the state transition models. The incremental life-year (LY) and QALY between the Osimertinib and pemetrexed-platinum cohorts for each modeling approach were estimated over seven years.
RESULTS
The PSM and 3-STM produced similar incremental LY (0.889 and 0.899, respectively) and QALY (0.827 and 0.840, respectively). However, 5-STM, which considered brain metastasis as separate health states, yielded a slightly higher incremental LY (0.910) but lower incremental QALY (0.695) than PSM and 3-STM.
CONCLUSIONS
Our findings indicate that incorporating additional health states such as brain metastases into economic models can have a considerable impact on incremental QALY estimates. To ensure appropriate health technology assessment decisions, comparison and justification of different modeling approaches are recommended in the economic evaluation of anticancer drugs.
Topics: Humans; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Platinum; Lung Neoplasms; Antineoplastic Agents; Cost-Benefit Analysis; Brain Neoplasms; Quality-Adjusted Life Years; Acrylamides; Aniline Compounds; Indoles; Pyrimidines
PubMed: 38336654
DOI: 10.1186/s12885-024-11971-x -
Heliyon Jan 2024Rearranged during transfection () gene fusion is a target for non-small cell lung cancer (NSCLC) treatment, and RET inhibitors are approved for advanced NSCLC. The role...
BACKGROUND
Rearranged during transfection () gene fusion is a target for non-small cell lung cancer (NSCLC) treatment, and RET inhibitors are approved for advanced NSCLC. The role of immune checkpoint inhibitors (ICIs) in fusion-positive NSCLC remains controversial. This retrospective study analyzed the efficacy of ICIs and RET inhibitors in Chinese patients with fusion-positive NSCLC.
METHODS
Data from patients diagnosed with advanced NSCLC harboring fusion from Jan 2017 to Sep 2021 were analyzed. Clinicopathological characteristics and outcomes of ICIs and RET inhibitors treatments were collected.
RESULTS
Seventy-five patients with fusion-positive advanced NSCLC were identified. The median age of patients was 57 years, half of the patients were female (50.3%), and most were non-smokers or light smokers (72%). Of the cancer types diagnosed in study patients, the fusion subtype accounted for 73.3% (55/75), twelve patients (16%) had fusion, and three (4%) had fusion. Sixteen patients were treated with ICIs. In previously untreated patients, we observed an objective response rate (ORR) of 71.4% and median progression free survival (PFS) of 7.5 months in seven assessable patients. Of four patients with PD-L1 overexpression (>50%) one received pembrolizumab and the other three patients received pemetrexed, carboplatin, and pembrolizumab or camrelizumab. In these patients, the ORR was 75% and disease control rate was 100%. Fifteen patients received selective RET inhibitors (pralsetinib and selpercatinib), resulting in an ORR of 53.3% (8/15) and median PFS of 10.0 months (95% CI 5.2-14.9).
CONCLUSIONS
ICIs for PD-L overexpression and treatment naive patients offer comparable benefits for fusion-positive NSCLC, warranting further investigation.
PubMed: 38304763
DOI: 10.1016/j.heliyon.2024.e24796 -
Cureus Jan 2024Immune checkpoint inhibitors have been a therapeutic oncological breakthrough in managing diverse malignancies. We present a 78-year-old male with stage IIIb non-small...
Immune checkpoint inhibitors have been a therapeutic oncological breakthrough in managing diverse malignancies. We present a 78-year-old male with stage IIIb non-small cell lung cancer (NSCLC) managed by concurrent chemotherapy with carboplatin/pemetrexed and radiotherapy followed by monthly durvalumab injections. He presented to the hospital with shortness of breath and fluid overload after eight months of starting durvalumab. Workup, including laboratory investigations, coronary angiography, and stress myocardial magnetic resonance imaging, increased our suspicion for the diagnosis of durvalumab-induced myocarditis and nonischemic dilated cardiomyopathy. He was managed with aggressive diuresis and pulse dose steroids with an improvement in his symptoms and his cardiac function. This case illustrates an under-reported clinical side effect in the era of advancement in oncological immunotherapy.
PubMed: 38298285
DOI: 10.7759/cureus.51456 -
Journal of Cancer Research and Clinical... Jan 2024There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic...
PURPOSE
There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.
METHODS
The study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.
RESULTS
Of the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35-0.83), WT1 (1.75, 1.06-2.90), calretinin (2.09, 1.14-3.84) expression and favourable panel (0.50, 0.27-0.92) was associated with prognosis.
CONCLUSIONS
The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.
Topics: Humans; WT1 Proteins; Calbindin 2; Lung Neoplasms; Tumor Suppressor Proteins; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Wilms Tumor; Kidney Neoplasms; Biomarkers; Biomarkers, Tumor; Ubiquitin Thiolesterase
PubMed: 38280040
DOI: 10.1007/s00432-023-05565-6 -
Experimental and Therapeutic Medicine Feb 2024Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with...
Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.
PubMed: 38274345
DOI: 10.3892/etm.2024.12370 -
Frontiers in Immunology 2023Pleural mesothelioma (PM) is an aggressive and rare disease, characterized by a very poor prognosis. For almost two decades, the world standard treatment regimen for... (Review)
Review
Pleural mesothelioma (PM) is an aggressive and rare disease, characterized by a very poor prognosis. For almost two decades, the world standard treatment regimen for unresectable PM has consisted of a platinum-based drug plus pemetrexed, leading to an overall survival of approximately 12 months. The dramatic therapeutic scenario of PM has recently changed with the entry into the clinic of immune checkpoint inhibition, which has proven to be an effective approach to improve the survival of PM patients. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced PM.
Topics: Humans; Mesothelioma; Mesothelioma, Malignant; Immunotherapy; Pleural Neoplasms; Pemetrexed
PubMed: 38259475
DOI: 10.3389/fimmu.2023.1333661 -
International Journal of Molecular... Jan 2024Folate receptor α (FR) was discovered many decades ago, along with drugs that target intracellular folate metabolism, such as pemetrexed and methotrexate. Folate is... (Review)
Review
Folate receptor α (FR) was discovered many decades ago, along with drugs that target intracellular folate metabolism, such as pemetrexed and methotrexate. Folate is taken up by the cell via this receptor, which also targeted by many cancer agents due to the over-expression of the receptor by cancer cells. FR is a membrane-bound glycosyl-phosphatidylinositol (GPI) anchor glycoprotein encoded by the folate receptor 1 (FOLR1) gene. FR plays a significant role in DNA synthesis, cell proliferation, DNA repair, and intracellular signaling, all of which are essential for tumorigenesis. FR is more prevalent in cancer cells compared to normal tissues, which makes it an excellent target for oncologic therapeutics. FRα is found in many cancer types, including ovarian cancer, non-small-cell lung cancer (NSCLC), and colon cancer. FR is widely used in antibody drug conjugates, small-molecule-drug conjugates, and chimeric antigen-receptor T cells. Current oncolytic therapeutics include mirvetuximab soravtansine, and ongoing clinical trials are underway to investigate chimeric antigen receptor T cells (CAR-T cells) and vaccines. Additionally, FRα has been used in a myriad of other applications, including as a tool in the identification of tumor types, and as a prognostic marker, as a surrogate of chemotherapy resistance. As such, FRα identification has become an essential part of precision medicine.
Topics: Humans; Folate Receptor 1; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Precision Medicine; Folic Acid; Glycosylphosphatidylinositols
PubMed: 38256120
DOI: 10.3390/ijms25021046 -
Medicine Dec 2023Many studies have shown that first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors are less effective in patients with epidermal... (Review)
Review
First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review.
RATIONALE
Many studies have shown that first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors are less effective in patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. The efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors is still under investigation. Although new targeted tyrosine kinase inhibitors and monoclonal antibody-based agents have made significant advances in the treatment of epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) mutation, the efficacy of these novel agents is not quite satisfactory. Platinum- and pemetrexed-based chemotherapy remains the standard first-line treatment for patients harboring EGFR ex20ins mutation.
PATIENT CONCERNS
We report for the first time 2 Chinese patients diagnosed with advanced lung adenocarcinoma with EGFR ex20ins mutations after analysis of the αC-helix sequence by next-generation sequencing. Both patients were treated with furmonertinib as the first-line therapy.
INTERVENTIONS
The first case included a 38-year-old female who had an EGFR ex20ins mutation (p.S768_D770dupSVD). After 1 month of treatment with furmonertinib, her symptoms of pain and cough were significantly alleviated. She achieved a partial response according to response evaluation criteria in solid tumors.[1] The final progression-free survival was 8.13 months. The second case included a 40-year-old male who had an EGFR ex20ins mutation (p.N771_P772insVal). He had a good response to furmonertinib and exhibited stable disease according to response evaluation criteria in solid tumors with a progression-free survival of 10.90 months.
OUTCOMES
Both patients experienced significant improvement in symptoms and prolonged survival after furmonertinib was used as first-line treatment. Side effects were limited but manageable.
CONCLUSION
The present study indicates that furmonertinib may be a first-line treatment option for patients with non-small cell lung cancer harboring EGFR ex20ins mutation.
Topics: Humans; Male; Female; Adult; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutagenesis, Insertional; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Adenocarcinoma of Lung; ErbB Receptors; Mutation; Exons; Indoles; Pyridines; Pyrimidines
PubMed: 38206746
DOI: 10.1097/MD.0000000000036667 -
JTCVS Open Dec 2023To evaluate the efficacy of multimodality treatment including extended pleurectomy/decortication (P/D) and hyperthermic intraoperative chemotherapy (HIOC) with cisplatin...
OBJECTIVE
To evaluate the efficacy of multimodality treatment including extended pleurectomy/decortication (P/D) and hyperthermic intraoperative chemotherapy (HIOC) with cisplatin for malignant pleural mesothelioma (MPM), we investigated the pharmacokinetics of platinum, adverse events after HIOC, and survival outcome.
METHODS
Fifty-three patients with pathologically diagnosed MPM (cT1-3N0-1M0, excluding sarcomatoid) underwent an extended P/D and HIOC (cisplatin 80 mg/m in saline 2 L, 42°C, 60 minutes) since 2011. The protocol includes postoperative 4 cycles of cisplatin and pemetrexed. Platinum concentrations in the perfusate (before and after) and the serum (1, 2, 4, 8, 24, 48, 72 hours after perfusion) were measured in 10 patients. Mortality and morbidity, especially adverse events of renal function, were investigated, and survival and affecting factors were examined.
RESULTS
All patients obtained macroscopic complete resection and pathologic staging revealed as follows: T1/2/3/4: 12/8/23/10, N0/1: 36/17, stage 1A/1B-3A/3B: 12/31/10, respectively. Platinum concentrations in the perfusate indicated that 28% of the dose remained in the pleural cavity, and the maximum concentration in the serum was 0.91 μg/mL. Six patients (11%) showed elevated max-creatinine (>2 mg/dL) postoperatively. Two patients (4%) received renal-replacement therapy, and one was weaned before discharge. There was no 30-day mortality and one in-hospital death (1.9%). Forty-six patients (87%) received multiple cycles of perioperative systemic chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 52.4 months and 18.7 months. Patents with stage 1A demonstrated a 5-year OS of 67.3% and a median DFS of 67.1 months, and patients with stage 1B-3A demonstrated a 5-year OS of 50.1% and a median DFS of 20.4 months. Univariate analysis showed histological subtype, p-T, p-stage, and multimodality treatment as significant factors affecting OS. Multivariate analysis revealed histology, p-stage, and multimodality as independent.
CONCLUSIONS
Extended P/D and HIOC with cisplatin for MPM is acceptable with limited acute kidney injury. This multimodality protocol provides promising favorable survival for stage 1A-3A disease.
PubMed: 38204668
DOI: 10.1016/j.xjon.2023.09.005 -
Cancer Reports (Hoboken, N.J.) Feb 2024Immune checkpoint inhibitors have been reported to have excellent therapeutic effects on various malignant tumors. However, immune-related adverse events can occur,...
BACKGROUND
Immune checkpoint inhibitors have been reported to have excellent therapeutic effects on various malignant tumors. However, immune-related adverse events can occur, targeting various organs.
CASE PRESENTATION
A 49-year-old male with lung carcinoma was started on carboplatin + pemetrexed + nivolumab (every 3 weeks) + ipilimumab (every 6 weeks), and nivolumab/ipilimumab was administered in the 3rd course. Subsequently, fever and fatigue developed, and grade 3 liver damage was also noted, so he was admitted to Kindai University Hospital. A bone marrow aspirate examination was performed on the third day of illness, and a definitive diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made. It was determined that immediate therapeutic intervention was necessary, and pulse therapy with methylprednisolone was started on the third day of illness. After 3 days of pulse treatment, a rapid recovery of platelet values, a decrease in ferritin levels, and a decrease in lactate dehydrogenase were observed. Subjective symptoms such as fever and fatigue also quickly improved.
CONCLUSION
Early diagnosis and treatment for HLH resulted in a positive response. The number of HLH cases may increase in the future due to the expansion of immune checkpoint inhibitor indications.
Topics: Male; Humans; Middle Aged; Nivolumab; Ipilimumab; Lymphohistiocytosis, Hemophagocytic; Adenocarcinoma of Lung; Lung Neoplasms; Steroids
PubMed: 38196303
DOI: 10.1002/cnr2.1960