Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset

Yuichiro Ohe, Fumio Imamura, Naoyuki Nogami, Isamu Okamoto, Takayasu Kurata, Terufumi Kato, Shunichi Sugawara, Suresh S Ramalingam, Hirohiko Uchida, Rachel Hodge, Sarah L Vowler, Andrew Walding, Kazuhiko Nakagawa, Yuichiro Ohe, Fumio Imamura, Naoyuki Nogami, Isamu Okamoto, Takayasu Kurata, Terufumi Kato, Shunichi Sugawara, Suresh S Ramalingam, Hirohiko Uchida, Rachel Hodge, Sarah L Vowler, Andrew Walding, Kazuhiko Nakagawa

Abstract

Background: The FLAURA study was a multicenter, double-blind, Phase 3 study in which patients with previously untreated epidermal growth factor receptor mutation-positive advanced non-small-cell lung carcinoma were randomized 1:1 to oral osimertinib 80 mg once daily or standard-of-care (gefitinib 250 mg or erlotinib 150 mg, once daily) to compare safety and efficacy. In the overall FLAURA study, significantly better progression-free survival was shown with osimertinib versus standard-of-care.

Methods: Selected endpoints, including progression-free survival (primary endpoint), overall survival, objective response rate, duration of response and safety were evaluated for the Japanese subset of the FLAURA study.

Results: In Japan, 120 eligible Japanese patients were randomized to osimertinib (65 patients) or gefitinib (55 patients) treatment from December 2014 to June 2017. Median progression-free survival was 19.1 (95% confidence interval, 12.6, 23.5) and 13.8 (95% confidence interval, 8.3, 16.6) months with osimertinib and gefitinib, respectively (hazard ratio, 0.61; 95% confidence interval, 0.38, 0.99). Median overall survival was not reached in either treatment arm (data were immature). In the osimertinib and gefitinib arms, objective response rate was 75.4% (49/65) and 76.4% (42/55), and median duration of response from onset was 18.4 (95% confidence interval, not calculated) and 9.5 (95% confidence interval, 6.2, 13.9) months, respectively. The incidence of adverse events was similar in the two groups. The frequency of Grade ≥3 interstitial lung disease and pneumonitis in the two groups were the same (one patient).

Conclusions: As the first-line therapy, osimertinib showed significantly improved efficacy versus gefitinib in the Japanese population of the FLAURA study. No new safety concerns were raised.

Clinical trial registration: NCT02296125 (ClinicalTrials.gov).

Figures

Figure 1.
Figure 1.
Disposition of the Japanese subset in the FLAURA study. DCO, data cutoff. aAmong patients who requested dispensing of crossover treatment with osimertinib, five patients provided dosing information with osimertinib in the electronic case report form.
Figure 2.
Figure 2.
PFS (A) and OS (B) in osimertinib and gefitinib treatment groups. *For reference purposes only. The P value is nominal as the present subgroup analysis was not powered for the Japanese subset analysis. CI, confidence interval; HR, hazard ratio; NC, not calculable; OS, overall survival; PFS, progression-free survival.
Figure 3.
Figure 3.
DoR in osimertinib and gefitinib treatment groups. CI, confidence interval; NC, not calculable; DoR, duration of response.

References

    1. Hanna N, Johnson D, Temin S, et al. . Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol 2017;35:3484–515.
    1. Novello S, Barlesi F, Califano R, et al. . Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27:v1–27.
    1. Lee CK, Davies L, Wu YL, et al. . Gefitinib or erlotinib vs chemotherapy for EGFR mutation-positive lung cancer: individual patient data meta-analysis of overall survival. J Natl Cancer Inst 2017;109:10.1093/jnci/djw279.
    1. Oxnard GR, Arcila ME, Sima CS, et al. . Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res 2011;17:1616–22.
    1. Yu HA, Arcila ME, Rekhtman N, et al. . Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013;19:2240–7.
    1. Jenkins S, Yang JC, Ramalingam SS, et al. . Plasma ctDNA analysis for detection of the EGFR T790M mutation in patients with advanced non-small cell lung cancer. J Thorac Oncol 2017;12:1061–70.
    1. Yang JC, Ahn MJ, Kim DW, et al. . Osimertinib in pretreated T790M-positive advanced non-small-cell lung cancer: AURA study phase II extension component. J Clin Oncol 2017;35:1288–96.
    1. Ballard P, Yates JW, Yang Z, et al. . Preclinical comparison of osimertinib with Other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res 2016;22:5130–40.
    1. Cross DA, Ashton SE, Ghiorghiu S, et al. . AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014;4:1046–61.
    1. Mok T, Ahn MJ, Hanet JY, et al. . CNS response to osimertinib in patients (pts) with T790M-positive advanced NSCLC: data from a randomized phase III trial (AURA3). J Clin Oncol 2017;35:9005.
    1. Mok TS, Wu Y-L, Ahn M-J, et al. . Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 2017;376:629–40.
    1. FDA TAGRISSO (osimertinib). Highlights of prescribing information. (26 April 2018, date last accessed).
    1. EMA Tagrisso (osimertinib). Summary of Product Characteristics. (June 2018, date last accessed).
    1. Soria JC, Ohe Y, Vansteenkiste J, et al. . Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018;378:113–25.
    1. Maemondo M, Inoue A, Kobayashi K, et al. . Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380–8.
    1. Mitsudomi T, Morita S, Yatabe Y, et al. . Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121–8.
    1. Han B, Tjulandin S, Hagiwara K, et al. . EGFR mutation prevalence in Asia-Pacific and Russian patients with advanced NSCLC of adenocarcinoma and non-adenocarcinoma histology: The IGNITE study. Lung Cancer 2017;113:37–44.
    1. Liu L, Liu J, Shao D, et al. . Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in East Asian patients. Cancer Sci 2017;108:2487–94.
    1. Ando M, Okamoto I, Yamamoto N, et al. . Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2006;24:2549–56.
    1. Kudoh S, Kato H, Nishiwaki Y, et al. . Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med 2008;177:1348–57.
    1. Batson S, Mitchel SA, Windisch R, et al. . Tyrosine kinase inhibitor combination therapy in first-line treatment of non-small-cell lung cancer: systematic review and network meta-analysis. Onco Targets Ther 2017;10:2473–82.
    1. Yang JC, Schuler MH, Yamamoto N, et al. . LUX-Lung 3: a randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 2012;30:10.1200/jco.2012.30.18_suppl.lba7500.
    1. Wu YL, Zhou C, Hu CP, et al. . Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014;15:213–22.
    1. Park K, Tan EH, O’Byrne K, et al. . Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016;17:577–89.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi