scholarly journals RET Inhibitors in Non-Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4415
Author(s):  
Priscilla Cascetta ◽  
Vincenzo Sforza ◽  
Anna Manzo ◽  
Guido Carillio ◽  
Giuliano Palumbo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Good Tolerability ◽  
Phase Ii Studies ◽  
Nsclc Patients

RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

Randomized Trial Comparing Cisplatin, Gemcitabine, and Vinorelbine With Either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Advanced Non–Small-Cell Lung Cancer: Interim Analysis of a Phase III Trial of the Southern Italy Cooperative Oncology Group

2000 ◽  
Vol 18 (7) ◽  
pp. 1451-1457 ◽  
Author(s):  
Pasquale Comella ◽  
Giuseppe Frasci ◽  
Nicola Panza ◽  
Luigi Manzione ◽  
Giuseppe De Cataldis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Interim Analysis ◽  
Stage Iv ◽  
Small Cell ◽  
Phase Iii ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Nsclc Patients

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non–small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of ≤ 70 years, and an Eastern Cooperative Oncology Group performance status ≤ 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m2, gemcitabine 1,000 mg/m2, and vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m2 on days 1 and 29 and vinorelbine 30 mg/m2/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P < .01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

Results of phase III trial of rh-endostatin (YH-16) in advanced non-small cell lung cancer (NSCLC) patients

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 7138-7138 ◽  
Author(s):  
Y. Sun ◽  
J. Wang ◽  
Y. Liu ◽  
X. Song ◽  
Y. Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Nsclc Patients
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