First-line immune-chemotherapy combination for squamous NSCLC is already a reality.
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ABSTRACT:
SUBMITTER: Hendriks LEL
PROVIDER: S-EPMC7354107 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
First-line immune-chemotherapy combination for squamous NSCLC is already a reality.
Hendriks Lizza E L LEL Menis Jessica J Remon Jordi J
Translational lung cancer research 20200601 3
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Project description:IntroductionWe present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC.MethodsPatients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mg/m2 (d 1) and 500 mg/m2 (d 8), cisplatin 75 mg/m2 (d 1), and gemcitabine 1250 mg/m2 (d 1 and 8) for four 3-week cycles, followed by avelumab 800 mg and cetuximab 500 mg/m2 every 2 weeks. The primary end point was the best overall response; the secondary end points were progression-free survival, duration of response, overall survival, and safety. Efficacy analyses were reported from an updated data cutoff.ResultsA total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% [95% confidence interval: 21.0%-50.9%]), and the median duration of response was 7.1 months (95% confidence interval: 4.2-12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event.ConclusionsThe combination of avelumab + cetuximab and chemotherapy showed antitumor activity and tolerable safety; however, the ORR was not improved compared with those reported for current standards of care (NCT03717155).
| S-EPMC9883276 | biostudies-literature
Project description:BackgroundThe safety and efficacy of combination of gefitinib with chemotherapy and bevacizumab in treatment patients with epidermal growth factor receptor (EGFR) mutations are currently unknown. This study was designed to evaluate the safety and preliminary efficacy of a combination therapy consisting of gefitinib, bevacizumab, pemetrexed, and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations.MethodsEligible patients with EGFR-mutated advanced non-squamous NSCLC were recruited and received gefitinib combination with bevacizumab plus pemetrexed and carboplatin treatment. The primary endpoints were safety and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS).ResultsFrom June 2019 to June 2021, 20 patients were enrolled in this study. The median follow-up was 33.8 months (95% CI, 31.0-36.6). Grade ≥ 3 adverse events was 65%, including neutropenia (30%), thrombocytopenia (20%), nausea (20%), skin rash (20%), bleeding (10%), and increased ALT (10%). There was no death related to toxicity occurred. The median PFS was 28 months (95% CI, 20.4-35.6). the ORR was 95% (95% CI, 75.1-99.9%), the DCR was 100% (95% CI, 83.2-100%), and the median DOR was 26.4 months (95% CI, 18.9-33.9). The median OS has not been reached.ConclusionThe results of this study demonstrate that the four-drug combination regimen, led by gefitinib, is manageable and tolerated and effective for patients with EGFR-mutated advanced non-squamous NSCLC.
| S-EPMC11520869 | biostudies-literature
Project description:IntroductionPembrolizumab plus carboplatin and (nab-)paclitaxel (pembrolizumab-chemotherapy) is currently an approved and recommended systemic therapy for patients with previously untreated advanced squamous NSCLC. This retrospective study evaluated real-world time on treatment (rwToT) and overall survival (OS) among patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy at oncology practices in the United States.MethodsUsing a real-world database, we selected adult patients with newly diagnosed or recurrent advanced squamous NSCLC (unresectable stages IIIB, IIIC, or IV) and good performance status (Eastern Cooperative Oncology Group 0-1) who initiated first-line pembrolizumab-chemotherapy from November 1, 2018, to May 31, 2020. The Kaplan-Meier method was used to determine rwToT and OS overall and by programmed death-ligand 1 (PD-L1) expression. Data cutoff was October 31, 2021.ResultsOf 364 eligible patients, 243 (67%) were men; median age was 70 (range: 43-84) years; and PD-L1 expression was greater than or equal to 1%, less than 1%, and unknown for 172 (47%), 94 (26%), and 98 patients (27%), respectively. Median follow-up from pembrolizumab-chemotherapy initiation to data cutoff was 26.2 months. Overall, median pembrolizumab rwToT was 6.5 months (95% confidence interval [CI]: 5.6-7.6), with on-treatment rates of 29.3% and 15.9% at 12 and 24 months, respectively. Median OS was 15.3 months (95% CI: 11.7-18.6), with 12- and 24-month OS rates of 54.9% and 37.3%, respectively. Median OS did not differ with PD-L1 expression: 16.2 months (95% CI: 10.3-20.6) for PD-L1 greater than or equal to 1% and 17.2 months (95% CI: 10.8-20.6) for PD-L1 less than 1%.ConclusionsFor patients with advanced squamous NSCLC and good performance status treated with first-line pembrolizumab-chemotherapy, rwToT and OS are similar to clinical trial findings for treatment duration and OS.
| S-EPMC9900616 | biostudies-literature
Project description:The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR?=?0.81, 95% CI 0.69-0.95, P?=?0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P?=?0.02). In selected patients by EGFR-mutation, both mutation positive (HR?=?0.48, 95% CI 0.28-0.83, P?=?0.009) and negative (HR?=?0.84, 95% CI 0.72-0.98, P?=?0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P?=?0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR?=?0.51, 95% CI 0.35-0.74, P?=?0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR?=?2.01, 95% CI 1.11-3.63; P?=?0.02) and diarrhea (RR?=?2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.
| S-EPMC3827342 | biostudies-literature
Project description:ObjectiveWe aimed to evaluate the cost-effectiveness of camrelizumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) without targetable epidermal growth factor receptor or anaplastic lymphoma kinase genetic aberrations in patients in China.MethodsA partitioned survival model was constructed to estimate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC from a Chinese healthcare perspective. Survival analysis was performed to calculate the proportion of patients in each state using data from trial NCT03134872. The cost of drugs was obtained from Menet, and the cost of disease management was obtained from local hospitals. Health state data were obtained from published literature. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were adopted to verify the robustness of the results.ResultsCompared with chemotherapy alone, camrelizumab plus chemotherapy provided 0.41 incremental quality-adjusted life years (QALYs) at an incremental cost of $10,482.12. Therefore, the incremental cost-effectiveness ratio of camrelizumab plus chemotherapy was $25,375.96/QALY from the Chinese healthcare perspective, much lower than three times the GDP per capita of China in 2021 ($35,936.09) as the willingness-to-pay threshold. The DSA indicated that the incremental cost-effectiveness ratio was most sensitive to the utility value of progression-free survival, followed by the cost of camrelizumab. The PSA illustrated that camrelizumab had 80% probability of being cost-effective at the threshold of $35,936.09 per QALY gained.ConclusionThe results suggest that camrelizumab plus chemotherapy is a cost-effective choice in the first-line treatment for patients with non-squamous NSCLC in China. Although this study has limitations such as short time of use of camrelizumab, no adjustment of Kaplan-Meier curves and the median overall survival that has not been reached, the difference in results caused by these factors is relatively small.
| S-EPMC9971596 | biostudies-literature
Project description:ObjectiveResults of CameL-sq has revealed the clinical benefits to patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). This study aims to evaluate the cost-effectiveness of camrelizumab plus chemotherapy to treat sq-NSCLC from the perspective of the Chinese healthcare system.MethodsWe used a partitioned survival model with a lifetime horizon to evaluate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in treating sq-NSCLC. Baseline characteristics of patients and key clinical data were extracted from CameL-sq. Costs and utilities were collected from the open-access database and published literature. Costs, quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICERs) were chosen as economic outcome indicators. We also performed a sensitivity analysis, subgroup analysis, and scenario analysis to verify the stability of the basic analysis results and explore the results under different scenarios.ResultsCombination therapy added 0.47 QALYS and 0.91 life-years with an incremental cost of $6,347.81 compared with chemotherapy, which had an ICER of $13,572 per QALY. The probabilistic sensitivity analysis indicated that camrelizumab plus chemotherapy had a 37.8% probability of cost-effectiveness at a willingness-to-pay threshold (WTP) of 1 time GDP per capital. When WTP was set as 3 times GDP per capital, combination therapy had significant cost-effectiveness. Deterministic sensitivity analysis showed that cost of the best supportive care was the factor with the greatest influence. The subgroup analysis found that combination therapy was associated with cost-effectiveness in several subgroups, namely, patients with disease stage IIIB/IIIC and with PD-L1 tumor proportion score ≤ 1%. Scenario analysis showed that ICER was positively correlated with the price of camrelizumab.ConclusionIn this economic evaluation, camrelizumab plus chemotherapy was unlikely to be cost-effective compared with chemotherapy in the first line therapy of sq-NSCLC from a perspective of the Chinese healthcare system. Reducing the price of camrelizumab and tailoring treatments based on individual patient factors might improve the cost-effectiveness. Our findings may provide evidence for clinicians in making optimal decisions in general clinical practice.
| S-EPMC9423383 | biostudies-literature
Project description:BackgroundThe necessity of platinum-doublet chemotherapy in first-line immunotherapy for non-squamous non-small cell lung cancer (nsqNSCLC) with programmed death-ligand 1 (PD-L1) expression on less than 50% of tumor cells remains poorly investigated. Biomarkers predicting this necessity can guide chemotherapy-free treatment to minimize unnecessary toxicity.MethodsTreated with immune checkpoint inhibitor monotherapy (ICI-mono), chemotherapy, or combination (ICI-chemo), 790 low PD-L1-expressing nsqNSCLCs (in-house: n=83; public: n=707) were analyzed for development and validation of the interaction score for additional chemotherapy (ISAC). Transcriptomic (public, n=11) and multiplex immunofluorescence data (in-house, n=100) were analyzed to evaluate the immune microenvironment.ResultsICI-chemo, compared with ICI-mono, tended to prolong progression-free survival (PFS; HR=0.72, p=0.004) and overall survival (OS; HR=0.77, p=0.071) as first-line therapy in low PD-L1-expressing nsqNSCLCs. The added value of chemotherapy was observed in the ISAC-low subgroup (PFS: HR=0.48, p<0.001; OS: HR=0.53, p=0.001) rather than the ISAC-high subgroup (PFS: HR=1.08, p=0.65; OS: HR=1.14, p=0.56). This predictive utility was independent of tumor mutational burden and PD-L1 expression, indicated by subgroup and multivariable analyses. A high ISAC was associated with adaptive immune resistance reflected by more proinflammatory (eg, CD8+ T cells and M1 macrophages) rather than anti-inflammatory tumor-infiltrating immune cells (eg, M2 macrophages) and high expression of immune checkpoints except for PD-L1 (eg, programmed cell death protein-1).ConclusionA high ISAC was identified as a significant predictor for virtually no added value of platinum-doublet chemotherapy for first-line ICI treatment in low PD-L1-expressing nsqNSCLC. Our findings may help refine personalized therapeutic strategies for nsqNSCLC, thereby improving efficacy and reducing undue toxicity.
| S-EPMC11624766 | biostudies-literature
Project description:Background and objectiveSintilimab has superior efficacy and safety in patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC), but its cost-effectiveness in China is unclear. This study is to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for locally advanced or metastatic squamous NSCLC in China.MethodsFrom the perspective of the Chinese health system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime time horizon. The two-stage method was used to estimate the overall survival hazard ratios to avoid the bias by crossover design in ORIENT-12 and KEYNOTE-407 studies. The anchored matching adjusted indirect comparison method (MAIC) was used for indirect comparison based on the individual patient data from ORIENT-12 and the publicly published KEYNOTE-407 study due to the lack of head-to-head clinical trials. Only direct medical costs were included, and utilities were derived from the published literature in the base case analysis. Sensitivity analysis was also performed to verify the robustness of the model results. In addition, the scenario analysis where the utilities were derived from the Quality of Life Questionnaire-Core 30 (QLQ-C30) scale in the ORIENT-12 by mapping to the EuroQol-5-dimension 5-level (EQ-5D-5L) was carried out to explore the uncertainty of the results.ResultsCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy incurred a lower lifetime cost ($12,321 vs. 36,371) and yielded fewer quality-adjusted life-years (QALYs) (0.9902 vs. 1.0085), which resulted in an incremental cost-effectiveness ratio (ICER) of $1,314,208/QALY. A sintilimab strategy is a cost-effectiveness option under the WTP of 1-3 times the GDP per capita in China ($11,250/QALY~$33,749/QALY). The utility value of the post-progression, the unit cost of albumin paclitaxel, and the utility value of the progression-free state were the main drivers in the deterministic sensitivity analysis (DSA). According to the probabilistic sensitivity analysis (PSA), sintilimab + chemotherapy was 100% cost-effective when the WTP was 1-3 times China's per capita GDP. The results of the scenario analysis showed that sintilimab + chemotherapy obtained more QALYs (1.2319 vs. 1.1815) and lower costs ($12,321 vs. 36,371), which implied that sintilimab + chemotherapy may dominate the pembrolizumab + chemotherapy.ConclusionCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy is more cost-effective for first-line treatment in Chinese patients with locally advanced or metastatic squamous NSCLC.
| S-EPMC9395965 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to estimate the cost-effectiveness of sugemalimab plus chemotherapy (SC) vs. placebo plus chemotherapy (PC), as the first-line treatment for patients with non-small cell lung cancer (NSCLC) in China.Material and methodsA three-state Markov model with a cycle of 3 weeks was built to assess the incremental cost-effectiveness ratio (ICER) of SC vs. PC as first-line treatment for patients with NSCLC over a 10-year horizon from Chinese health care perspective. Time-dependency transition probability and safety data were derived from a multicenter, randomized, double-blind, phase 3 clinical trial performed in China (GEMSTONE-302). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) and the ICER under a willingness-to-pay (WTP) threshold of $37,663/QALYs. Deterministic, scenario and probabilistic sensitivity analysis were employed to investigate the robustness of model outcomes.ResultsIn base-case analysis, compared with PC, first-line SC for intention-to-treat (ITT) population gained an additional 0.57 QALYs with an incremental cost of $62,404.15, resulting in an ICER of $109,480.97/QALYs gained. When a patient assistance program (PAP) was available, the ICER decreased to $52,327.02/QALYs. In subgroup analysis, the ICER values were above the WTP threshold with or without PAP. Sensitivity analysis results suggested that the model outcomes were reliable.ConclusionFrom the perspective of Chinese healthcare system, the SC was not cost-effective in comparison to PC as first-line treatment for NSCLC, regardless of PD-L1 tumor expression level and pathological subtype.
| S-EPMC9670176 | biostudies-literature
Project description:BackgroundThe combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.MethodsEMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.ResultsA total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79) and rash (RR = 7.43, 95% CI = 4.56-12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93) and fatigue (RR = 9.60, 95% CI = 2.28-40.86) compared with EGFR TKI monotherapy.ConclusionsThe synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.
| S-EPMC4540576 | biostudies-literature