Efficacy and Safety of Ramucirumab With Docetaxel Versus Placebo With Docetaxel as Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer: A Subgroup Analysis According to Patient Age in the REVEL Trial

Purpose Trials combining irinotecan/docetaxel and irinotecan/gemcitabine in second-line treatment of non–small-cell lung cancer (NSCLC) have yielded promising results. Preliminary data suggested that the selective cyclooxygenase -2 inhibitor celecoxib (CBX) might enhance efficacy of chemotherapeutic regimens. This multicenter, phase II, randomized trial investigated efficacy and safety of irinotecan and docetaxel and irinotecan and gemcitabine, with or without CBX, in second-line treatment of NSCLC. Patients and Methods Patients 18 years or older were randomly assigned to receive irinotecan 60 mg/m2 and docetaxel 35 mg/m2, or irinotecan 100 mg/m2 and gemcitabine 1,000 mg/m2, with or without CBX 400 mg twice daily, for four cycles. Primary efficacy end points were median and 1-year survival probabilities. Patient-reported symptoms were assessed by the Lung Cancer Symptoms Scale (LCSS). Results A total of 133 patients were assessable for efficacy and safety. Median survival time was 6.31 months for patients treated with CBX and 8.99 months for those treated with chemotherapy alone. One-year survival rates were 24% and 36% respectively. The overall toxicity rates and LCSS scores were similar between patients treated or not treated with CBX. Four deaths were considered possibly treatment related. Conclusion Survival results for the second-line regimens in this study were similar to results reported for single-agent therapy in this setting. CBX did not appear to enhance efficacy or improve patient-reported symptoms. The addition of high-dose CBX to second-line chemotherapy in NSCLC cannot be recommended.

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The efficacy and safety profile of anlotinib plus docetaxel as second-line treatment in advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21068 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21068-e21068

Author(s):

Zhiqiao Xu ◽

Yan Zhang

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Objective Response ◽

Small Cell ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Small Cell Lung

e21068 Background: Docetaxel is a standard second line treatment in advanced NSCLC, but the treatment effect is limited. Previous studies, such as REVEL, demonstrated that anti angiogenic therapy combined with docetaxel had significantly therapeutic efficacy. Anlotinib is an oral multi target angiogenesis TKI targeting the VEGFR, FGFR, PDGFR and c Kit. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC, and this study aims to investigate the efficacy and safety of Anlotinib combined with docetaxel in second-line treatment in advanced non-small cell lung cancer (NSCLC). Methods: This is a single-center, single-arm clinical trial. A group of 30 patients of histologically or cytologically confirmed, locally advanced stage IIIB-IV NSCLC and with ECOG PS 0-1 were admitted to the Kaifeng Central Hospital Cancer Center. Patients who progressed after first-line treatment were treated with anlotinib (12 mg p.o., QD d1 to 14, q3w) combined with docetaxel (75mg/m2, iv, QD, d1 to 14, q3w) as the second-line therapy. The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 30 patients were enrolled from October 2018 to April 2020. At data cutoff (Sept. 30, 2020), 30 patients were available for efficacy analysis. The median progression-free survival (mPFS) was 7.5 months (2.0-18.5). Among these patients, there was 1 CR, 9 PR, 15 SD, 5 PD, resulting in the ORR = 33.33% and the DCR = 83.33%. The Cox multivariate analysis showed that stage is an independent risk factor affecting prognosis ( p= 0.003). The most common grade 3 AEs were leukopenia (23,3%), neutropenia (13.3%), hypertension (13.3%), which can be controlled, and no grade 4 or grade 5 AEs occurred. Conclusions: Second line anlotinib plus docetaxel showed clinical benefit in advanced NSCLC patients in terms of PFS, ORR and DCR, and the incidence of adverse reactions are tolerable. This combination might be a promising option for patients advanced NSCLC.

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Effect of anlotinib in advanced small cell lung cancer (SCLC) patients relapsed within three months after second-line treatment: A subgroup analysis from a randomized, double-blind phase II trial (ALTER 1202).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9063 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9063-9063

Author(s):

Jianhua Shi ◽

Ying Cheng ◽

Qiming Wang ◽

Kai Li ◽

Lin Wu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Subgroup Analysis ◽

Objective Response ◽

Small Cell ◽

Line Treatment ◽

Second Line ◽

Small Cell Lung ◽

Double Blind

9063 Background: Anlotinib had significantly improved progress-free survival (PFS) and overall survival (OS) of advanced small cell lung cancer (SCLC) patients received at least two lines chemotherapy in the ALTER 1202 trial. Here, we reported the effect of anlotinib in advance SCLC patients relapsed within 3 months after second-line treatment. Methods: The ALTER 1202 was a randomized, double-blind phase 2 trial including patients with advanced SCLC that received at least two previous lines of chemotherapy. Eligible patients were randomized in a 2:1 ratio to receive either anlotinib or placebo until tumor progression or unacceptable toxicity. The subgroup analysis assessed the effect of anlotinib in patients relapsed within 3 months after second-line treatment. The primary outcome was PFS. The secondary outcomes were OS, objective response rate (ORR), disease control rate (DCR) and safety. This trial was registered with ClinicalTrials.gov, number NCT03059797. Results: In the ALTER1202 trial, 67 patients in anlotinib group and 34 patients in placebo group relapsed within 3 months after second-line treatment. Among them, the median PFS was 3.98 months (95% confidence interval [CI], 2.79 to 4.24) with anlotinib versus 0.72 months (95% CI, 0.69 to 0.82) with placebo (hazard ratio [HR], 0.14; 95% CI, 0.08 to 0.26; P < 0.0001). Meanwhile, anlotinib significantly prolonged OS compared with placebo (7.29 months [95% CI, 6.51 to 10.51] versus 4.37 months [95% CI, 2.33 to 6.47]; HR, 0.42 [95% CI, 0.23 to 0.74]; P = 0.0059) in patients relapsed within 3 months after second-line treatment. ORR was 4.48% (3 PR) for anlotinib and 2.94% (1 PR) for placebo (P = 0.708). DCR was 73.13% for anlotinib and 11.76% for placebo (P < 0.0001). The most common adverse events were hypertension (38.81%), anorexia (28.36%), fatigue (22.39%) and Elevation of alanine aminotransferase (17.91%). Conclusions: Anlotinib improved PFS and OS in advanced SCLC patients relapsed within 3 months after second-line treatment and was well tolerated.

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