Overall response rate as a surrogate of progression-free survival with molecular targeted agents: A meta-analysis of phase III trials in advanced non-small cell lung cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19142-e19142
Author(s):  
Hiroaki Akamatsu ◽  
Keita Mori ◽  
Takashi Kikuchi ◽  
Hiroki Ueda ◽  
Keiichiro Akamatsu ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Targeted Agents ◽  
Small Cell Lung ◽  
Free Survival ◽  
Phase Iii Trials

Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer

Lung Cancer ◽  
2013 ◽  
Vol 79 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Etsuji Suzuki ◽  
Massimo Di Maio ◽  
Paolo Chiodini ◽  
Yoshiro Fujiwara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Targeted Agents ◽  
Small Cell Lung ◽  
Free Survival ◽  
Phase Iii Trials

scholarly journals Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non–Small-Cell Lung Cancer: METLung

2017 ◽  
Vol 35 (4) ◽  
pp. 412-420 ◽  
Author(s):  
David R. Spigel ◽  
Martin J. Edelman ◽  
Kenneth O’Byrne ◽  
Luis Paz-Ares ◽  
Simonetta Mocci ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival

Purpose The phase III OAM4971g study (METLung) examined the efficacy and safety of onartuzumab plus erlotinib in patients with locally advanced or metastatic non–small-cell lung cancer selected by MET immunohistochemistry whose disease had progressed after treatment with a platinum-based chemotherapy regimen. Patients and Methods Patients were randomly assigned at a one-to-one ratio to receive onartuzumab (15 mg/kg intravenously on day 1 of each 21-day cycle) plus daily oral erlotinib 150 mg or intravenous placebo plus daily oral erlotinib 150 mg. The primary end point was overall survival (OS) in the intent-to-treat population. Secondary end points included median progression-free survival, overall response rate, biomarker analysis, and safety. Results A total of 499 patients were enrolled (onartuzumab, n = 250; placebo, n = 249). Median OS was 6.8 versus 9.1 months for onartuzumab versus placebo (stratified hazard ratio [HR], 1.27; 95% CI, 0.98 to 1.65; P = .067), with a greater number of deaths in the onartuzumab arm (130 [52%] v 114 [46%]). Median progression-free survival was 2.7 versus 2.6 months (stratified HR, 0.99; 95% CI, 0.81 to 1.20; P = .92), and overall response rate was 8.4% and 9.6% for onartuzumab versus placebo, respectively. Exploratory analyses using MET fluorescence in situ hybridization status and gene expression showed no benefit for onartuzumab; patients with EGFR mutations showed a trend toward shorter OS with onartuzumab treatment (HR, 4.68; 95% CI, 0.97 to 22.63). Grade 3 to 5 adverse events were reported by 56.0% and 51.2% of patients, with serious AEs in 33.9% and 30.7%, for experimental versus control arms, respectively. Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non–small-cell lung cancer.

scholarly journals Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Tang ◽  
Longyu Jin ◽  
Zhang Zhang ◽  
Zhibin Jiang ◽  
Zeeshan Malik
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Overall Response Rate ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

ObjectiveTo systematically evaluate the efficacy and safety of alectinib versus crizotinib in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer.MethodsStudies about the efficacy of alectinib versus crizotinib in the treatment of ALK-positive non-small cell lung cancer were searched in PubMed, Scopus, Embase and the Cocharane Library from inception to February 15, 2020. Two reviewers independently screened these studies, extracted the data, assessed the risk of bias in the included studies by using the Cochrane risk assessment tool, and then used review manager 5.3 software for meta-analysis.ResultsThree studies comprising a total of 697 patients with ALK-positive non-small cell lung cancer were included, 380 in the alectinib group and 317 in the crizotinib group. The dose of alectinib (300 mg) in J-ALEX were lower than the approved dose (600 mg), however the crizotinib group in all three studies received the recommended dose (250 mg). Performance bias was high in all three studies whereas, and the attrition bias was high in two studies (Toyoaki Hida 2017 and Solange peters 2017). The results of meta-analysis showed that: the overall response rate [OR = 2.07, 95% CI (1.41, 3.06), P = 0.0002], the progression free survival [HR = 0.34, 95% CI (0.21, 0.55), P <0.0001], the partial response [OR = 1.71, 95% CI (1.19, 2.46), P = 0.003], P = 0.001], in alectinib group were higher than that of crizotinib group. Though the total number of events in complete response and the disease control rate were more in alectinib group than that of crizotinib group, the meta-analysis results shows no significant differences between two drugs in the disease control rate [OR = 2.24, 95% CI (0.56, 8.88), P = 0.25], the complete response [OR = 1.82, 95% CI (0.75, 4.45), P = 0.19]. In addition, the number of events in the stable disease [OR = 0.45, 95% CI (0.28, O.74), P = 0.001], and the adverse events [OR = 0.50, 95% CI (0.23, 0.81), P = <0.0001] in alectinib group were lower than that of crizotinib group.ConclusionAlectinib in terms of overall response rate, progression-free survival and partial response is superior to crizotinib in the treatment of ALK-positive non-small cell lung cancer and is well tolerated. Compared with crizotinib, alectinib is more effective than crizotinib and has a lower incidence of total adverse reactions. Meta-analysis results confirm the strong base for alectinib as a first-line treatment for ALK-positive NSCLC.

scholarly journals Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

2015 ◽  
Vol 33 (9) ◽  
pp. 1008-1014 ◽  
Author(s):  
Gideon M. Blumenthal ◽  
Stella W. Karuri ◽  
Hui Zhang ◽  
Lijun Zhang ◽  
Sean Khozin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Patient Level ◽  
Level Analysis

Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect.

Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol.

1995 ◽  
Vol 13 (6) ◽  
pp. 1425-1429 ◽  
Author(s):  
C Blanke ◽  
R Ansari ◽  
R Mantravadi ◽  
R Gonin ◽  
R Tokars ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Free Survival

PURPOSE Here we report the results of a phase III study, to evaluate whether the addition of cisplatin to radiation therapy (XRT) would improve progression-free survival or overall survival for patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Two hundred forty patients with biopsy-proven unresectable NSCLC without distant metastases or lower-stage medically inoperable patients were randomized to one of two treatment arms. Arm A consisted of thoracic XRT alone, 60 to 65 Gy total tumor dose in daily fractions of 1.80 to 2.00 Gy; and arm B consisted of identical XRT with the addition of cisplatin 70 mg/m2 every 3 weeks for three cycles beginning on the first day of irradiation. RESULTS Two hundred fifteen patients were eligible and assessable. The overall response rate was 50% on the combination arm versus 38% on the XRT-alone arm (P = .076). The median progression-free survival time was 23 versus 22 weeks, respectively (P = .0537). The median survival time was 43 weeks on the combination arm versus 46 weeks on the XRT arm (Poverall = .3469). The 1-, 2-, and 5-year survival rates were 43%, 18%, and 5% on the combination arm versus 45% 13%, and 2% on the XRT arm, respectively. CONCLUSION Cisplatin, administered every 3 weeks, does not significantly improve response rate, progression-free survival, or overall survival when added to thoracic XRT for locally advanced unresectable NSCLC.

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

scholarly journals Efficacy of S-1 after pemetrexed in patients with non-small cell lung carcinoma: a retrospective multi-institutional analysis

2021 ◽  
Author(s):  
Shinnosuke Takemoto ◽  
Kazumasa Akagi ◽  
Sawana Ono ◽  
Hiromi Tomono ◽  
Noritaka Honda ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Small Cell Lung Carcinoma ◽  
Progression Free Survival ◽  
Small Cell Lung ◽  
Confidential Interval ◽  
Cell Lung Carcinoma ◽  
Free Survival ◽  
Time To Treatment Failure ◽  
Nsclc Patients

Abstract Background: This study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. Methods: This retrospective study included patients with advanced (c-stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at 6 hospitals in Japan. Primary endpoint: Overall response rate (ORR). Secondary endpoint: Disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). Results: A total of 53 NSCLC patients met the criteria. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidential interval (CI): 0.00-10.1%). Median TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. Conclusion: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared to the historical control. It might be one of the choices to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

scholarly journals Prognostic value of the common tumour-infiltrating lymphocyte subtypes for patients with non-small cell lung cancer: A meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242173
Author(s):  
Benchao Chen ◽  
Heng Li ◽  
Chao Liu ◽  
Xudong Xiang ◽  
Shuting Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
High Density ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumour Nest ◽  
Disease Specific

Background Many previous studies have revealed that tumour-infiltrating lymphocytes (TILs) are significantly associated with prognosis in various tumours. However, this finding remains controversial in non-small cell lung cancer (NSCLC). We performed this meta-analysis systematically to evaluate the prognostic value of TILs in NSCLC. Methods The references were collected by searching the PubMed, EMBASE and Web of Science databases. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized using random or fixed effects models to evaluate the association between TILs and NSCLC survival outcomes. Results A total of 45 interrelated studies were eligible that included 11,448 patients. Pooled analysis showed that a high density of TILs indicated a better overall survival (HR = 0.80, 0.70–0.89) and progression-free survival (HR = 0.73, 0.61–0.85) for patients with NSCLC; a high density of CD3+ TILs in the tumour nest indicated a better overall survival (HR = 0.84, 0.69–0.99) and disease-specific survival (HR = 0.57, 0.34–0.80); a high density of CD4+ TILs in the tumor nest indicated a favourable overall survival (HR = 0.86, 0.76–0.96); a high density of CD8+ TILs indicated a favourable overall survival (HR = 0.995, 0.99–1.0), progression-free survival (HR = 0.52, 0.34–0.71), disease-free survival (HR = 0.64, 0.43–0.85), relapse/recurrence-free survival (HR = 0.42, 0.18–0.67) and disease-specific survival (HR = 0.56, 0.35–0.78); and a high density of CD20+ TILs in the tumour nest indicated a favourable overall survival (HR = 0.65, 0.36–0.94). However, a high density of Foxp3+ TILs in the tumour stroma indicated a worse relapse/recurrence-free survival (HR = 1.90, 1.05–2.76) in NSCLC. Conclusions Our meta-analysis confirmed that high densities of TILs, CD3+TILs, CD4+TILs, CD8+TILs and CD20+TILs in the tumour nest are favourable prognostic biomarkers for patients with NSCLC, and Foxp3+TILs in the tumour stroma are a poor prognostic biomarker.

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