LUX-Lung 4: A Phase II Trial of Afatinib in Patients With Advanced Non–Small-Cell Lung Cancer Who Progressed During Prior Treatment With Erlotinib, Gefitinib, or Both

2013 ◽  
Vol 31 (27) ◽  
pp. 3335-3341 ◽  
Author(s):  
Nobuyuki Katakami ◽  
Shinji Atagi ◽  
Koichi Goto ◽  
Toyoaki Hida ◽  
Takeshi Horai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Partial Response ◽  
Small Cell Lung Cancer ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung

Purpose New molecular targeted agents are needed for patients with non–small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after ≥ 12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R + T790M, and deletion in exon 19 + T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatment-related AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

Poziotinib for Patients With HER2 Exon 20 Mutant Non–Small-Cell Lung Cancer: Results From a Phase II Trial

2021 ◽  
pp. JCO.21.01113
Author(s):  
Yasir Y. Elamin ◽  
Jacqulyne P. Robichaux ◽  
Brett W. Carter ◽  
Mehmet Altan ◽  
Don L. Gibbons ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Exon 20

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients with advanced HER2 exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans were performed at least 28 days from initial radiologic response. RESULTS Thirty patients received poziotinib treatment. At baseline, 90% of patients received prior platinum-based chemotherapy and 53% had two lines or more prior systemic therapies. As of data cutoff on March 1, 2021, the confirmed objective response rate was 27% (95% CI, 12 to 46). Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable). The most common grade 3 treatment-related adverse events were skin rash (47%) and diarrhea (20%). There was one possible treatment-related death because of pneumonitis. CONCLUSION Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.

Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Fruquintinib After Two Prior Chemotherapy Regimens in Chinese Patients With Advanced Nonsquamous Non‒Small-Cell Lung Cancer

2018 ◽  
Vol 36 (12) ◽  
pp. 1207-1217 ◽  
Author(s):  
Shun Lu ◽  
Jianhua Chang ◽  
Xiaoqing Liu ◽  
Jianhua Shi ◽  
You Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Multicenter Phase

Purpose Patients with advanced non‒small-cell lung cancer (NSCLC) who fail two lines of chemotherapy have unmet medical needs. The kinase inhibitor fruquintinib selectively targets vascular endothelial growth factor receptors and, hence, tumor angiogenesis and lymphogenesis. This randomized, double-blind, placebo-controlled, multicenter phase II trial evaluated the efficacy and safety of fruquintinib in patients with advanced nonsquamous NSCLC who experienced disease progression after second-line chemotherapy. Patients and Methods Eligible patients were randomly assigned (two to one; stratified by epidermal growth factor receptor status) to receive fruquintinib or placebo, both in combination with best supportive care. Oral fruquintinib (5 mg once daily) was given in 4-week cycles of 3 weeks of treatment followed by 1 week off. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was progression-free survival (PFS) evaluated by a blinded image central review (BICR) committee. Secondary end points included investigator-evaluated PFS, objective response rate, disease control rate, overall survival, and safety. Results Ninety-one patients from 12 hospitals received treatment with fruquintinib (n = 61) or placebo (n = 30). Median PFS was 3.8 months with fruquintinib by both BICR and investigators’ evaluations (hazard ratio by BICR, 0.34; 95% CI, 0.20 to 0.57; P < .001). Three- and 6-month survival rates were 90.2% and 67.2% in the fruquintinib group and 73.3% and 58.8% in the placebo group, respectively. The objective response rate and disease control rate were 13.1% and 60.7% with fruquintinib, compared with 0% and 13.3% with placebo ( P = .041 and < .001), respectively. The most common treatment-emergent adverse events with fruquintinib (≥ grade 3) were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%). Conclusion Third- and fourth-line fruquintinib for advanced NSCLC was superior to placebo and had an acceptable safety profile.

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

1998 ◽  
Vol 16 (4) ◽  
pp. 1388-1396 ◽  
Author(s):  
J P Sculier ◽  
M Paesmans ◽  
J Thiriaux ◽  
J Lecomte ◽  
G Bureau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Randomized Trial ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Moderate Dose

PURPOSE A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

scholarly journals Disodium Cantharidinate and Vitamin B6 Injection Adjunct with Platinum-Based Chemotherapy for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhichao Wang ◽  
Fanchao Feng ◽  
Qi Wu ◽  
Yihan Jin ◽  
Cheng Gu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response Rate ◽  
Vitamin B6 ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
Karnofsky Performance Score ◽  
Performance Score ◽  
Small Cell Lung

Purpose. Disodium cantharidinate and vitamin B6 (DCVB6) injection is effective and widely used for the clinical treatment of non-small-cell lung cancer (NSCLC). This meta-analysis aimed to provide evidence-based medical data for clinical treatment with DCVB6 injection. Methods. We searched 7 medical databases up to January 2018 for all randomized controlled trials (RCTs) based on DCVB6 injection combined with chemotherapy in patients with NSCLC. A manual search in relevant journals and of relevant literature on other websites was also performed. Data extraction and quality assessment were conducted independently by two reviewers. Subsequently, a meta-analysis was conducted using RevMan 5.3 software. Pooled risk ratio (RR) with 95% confidence interval (CI) was used to evaluate dichotomous and continuous outcomes, respectively. The PROSPERO ID was CRD42018086377. Results. A total of 19 RCTs were included. The results of the meta-analysis indicated that the DCVB6 injection combined with chemotherapy was superior to chemotherapy alone regarding objective response rate (RR=1.58, 95% CI 1.40-1.79), Karnofsky performance score (RR=1.68, 95% CI 1.42-1.99), clinical symptom (RR=1.68, 95% CI 1.44-1.96), white blood cell toxicity (RR=0.36, 95% CI 0.27-0.49), platelet toxicity (RR=0.46, 95% CI 0.33-0.63), and vomiting (RR=0.50, 95% CI 0.37-0.67). Conclusions. The current evidence suggests that DCVB6 injection combined with chemotherapy could increase objective response rate and Karnofsky performance score, improve clinical symptoms, and reduce side effects caused by chemotherapy in patients with NSCLC. However, these results should be carefully interpreted due to the low-quality methodology and the small sample sizes of the trials, and our conclusions should be verified by high-quality, large-scale, double-blinded RCTs.

Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients.

1994 ◽  
Vol 12 (2) ◽  
pp. 360-367 ◽  
Author(s):  
T Le Chevalier ◽  
D Brisgand ◽  
J Y Douillard ◽  
J L Pujol ◽  
V Alberola ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Randomized Study ◽  
Objective Response ◽  
Multicenter Trial ◽  
Small Cell ◽  
Survival Duration ◽  
Small Cell Lung

PURPOSE We designed a prospective randomized trial to compare vinorelbine and cisplatin (NVB-P) with vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared with vinorelbine alone (NVB), an outpatient regimen, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-five centers included 612 patients in this study: 206 on NVB-P, 200 on VDS-P, and 206 on NVB. Vinorelbine was administered at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on days 1 and 29 and then every 6 weeks, and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Four percent of the patients entered were ineligible and 59% had metastatic disease. RESULTS An objective response rate was observed in 30% of patients in the NVB-P arm versus 19% in the VDS-P arm (P = .02) and 14% in the NVB arm (P < .001). The median duration of survival was 40 weeks in the NVB-P arm, compared with 32 weeks in the VDS-P arm and 31 weeks in the NVB arm. Comparison of survival among the three groups demonstrated an advantage for NVB-P compared with VDS-P (P = .04) and NVB (P = .01). Neutropenia was significantly higher in the NVB-P group (P < .001), and neurotoxicity was more frequent with VDS-P (P < .004). CONCLUSION Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a relevant regimen in advanced NSCLC.

Preoperative docetaxel and gemcitabine in resectable non-small cell lung cancer: A phase II trial of the Minnie Pearl Cancer Research Network

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18100-18100
Author(s):  
D. S. Thompson ◽  
D. R. Spigel ◽  
F. A. Greco ◽  
D. A. Yardley ◽  
H. A. Burris ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Small Cell ◽  
Preoperative Therapy ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Grade 3

18100 Background: Preoperative chemotherapy may improve outcomes for patients (pts) with resectable non-small cell lung cancer (NSCLC) compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative gemcitabine (G) and docetaxel (D) in pts with resectable NSCLC. Methods: The primary endpoint was to assess the pathologic response rate of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station = 2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Additional eligibility criteria: measurable disease, ECOG PS 0–1, and informed consent. Treatment: G 1,000 mg/m2 and D 30 mg/m2 days 1, 8 every 21 days x 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. If pts were inoperable, had incomplete resections, or N2 disease, D 20 mg/m2, carboplatin AUC=1.5 weekly x 7, and radiation to 63 Gy were administered. Analysis was by intent to treat. Results: Between April 2004 and September 2005, 75 pts were enrolled. Median age was 62 years. 92% of planned preoperative therapy was administered and 38 pts (51%) underwent resection. The clinical objective response rate was 30% (95% CI 20%-42%). No pathological complete responses were observed. 26 pts went on to receive chemoradiotherapy. Median progression-free survival was 9.8 months (95% CI 5.9–13.9). Median overall survival was 18 months (95% CI 14.8- 21.3). 71% of pts were alive at 1 year. Grade 3/4 hematologic toxicity with preoperative therapy included neutropenia (28%), anemia (4%), and thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity was limited. Conclusions: G/D is a well tolerated preoperative regimen for pts with resectable NSCLC, however did not result in pathologic complete responses. There is no suggestion that G/D is more active than other tested combined modality regimens. The role of preoperative therapy in NSCLC remains undefined. Additional studies comparing preoperative and adjuvant treatment are warranted. No significant financial relationships to disclose.

ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18017-e18017
Author(s):  
Kyohei Kaburaki ◽  
Fumiyoshi Ohyanagi ◽  
Azusa Tanimoto ◽  
Toshio Sakatani ◽  
Yuko Kawano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Response Rate ◽  
Fusion Gene ◽  
Objective Response ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.

scholarly journals Clinical Study of Gefitinib for Non-Small Cell Lung Cancer

2021 ◽  
Vol 5 (6) ◽  
pp. 47-51
Author(s):  
Yang Li
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Markers ◽  
Cell Lung Cancer ◽  
Adverse Reactions ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Drug

Objective: To evaluate the clinical efficacy of gefitinib in non-small cell lung cancer. Methods: A total of 45 patients with non-small cell lung cancer who received treatment in Taizhou Second People’s Hospital from January 2018 to January 2020 were selected as the subjects in this study, in which all of them were treated with gefitinib. Its efficacy and safety were evaluated. Results: The objective response rate was 53.33% and the disease control rate was 84.44%. After treatment, the levels of tumor markers were measured again, of which the levels of CA125 and CEA were significantly lower than before (P < 0.05). After treatment, the patients’ CD3+, CD4+, and CD4+/CD8+ were significantly lower than those before treatment, and CD8+ was significantly higher (P < 0.05). Conclusion: Gefitinib, which is a targeted therapy for non-small cell lung cancer, can reduce the level of serum tumor markers and improve the immune function. The curative effect is good, but more emphasis should be on the adverse reactions caused by a single drug use.

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