JOURNAL of
ONCOLOGICAL
SCIENCES

ORIGINAL RESEARCH ARTICLE

The Efficacy of Pemetrexed-Based Therapy in Advanced Lung Adenocarcinoma with Targetable Driver Mutation: A Real-Life Experience
Received Date : 19 Jun 2019
Accepted Date : 22 Nov 2019
Available Online : 10 Feb 2020
Doi: 10.37047/jos.2020-73476 - Article's Language: EN
J Oncol Sci. 2020;6(1):43-8
This is an open access article under the CC BY-NC-ND license
ABSTRACT
Objective: Lung adenocarcinoma is the most common subtype of non-small cell lung cancer, and also, approximately 25% of lung adenocarcinoma patients have targetable driver mutations. Despite several novel therapeutic advances in the treatment of lung adenocarcinoma with targetable driver mutations, chemotherapy still has an important role to play. In this study, we aimed to evaluate the realworld efficacy of pemetrexed-based chemotherapy in lung adenocarcinoma with the targetable mutation. Material and Methods: The advanced lung adenocarcinoma patients with targetable driver mutations who received pemetrexed-based chemotherapy between 2014 and 2018 were enrolled in this study, retrospectively. The patients were stratified according to mutation type and pemetrexed-line as pre or posttyrosine kinase inhibitor (TKI). The primary outcome of our study was considered as progression-free survival (PFS). Results: A total of 265 patients with the targetable mutation were screened and only 60 were enrolled in the study. In the entire group, the median PFS was 7.81. Median PFS was significantly higher in ALK-ROS1 positive subgroup than EGFR positive subgroup (p=0.001). The median PFS was higher in patients who received pre-TKI treatment in the ALK-ROS1 subgroup (p=0.006). In EGFR positive patients, PFS was similar between pre or post TKI groups (p=0.28). The overall response rate was 55%, 59.1%, and 52.6% in the entire group, ALK-ROS1 positive and EGFR positive subgroup, respectively. Conclusion: We showed that pemetrexed-based therapy is still an important choice for the patients who progress after targeted therapy and also for those who are not suitable for another targeted therapeutic agent.
KAYNAKLAR
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. [Crossref]  [PubMed] 
  2. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589-1597. [Crossref]  [PubMed] 
  3. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(1):3543-3551. [Crossref]  [PubMed] 
  4. Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012;13(3):247-255. [Crossref] 
  5. Schwartz LH, Litiere S, de Vries E, et al. RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer. Jul 2016;(62):132-137. [Crossref]  [PubMed]  [PMC] 
  6. Patil VM, Noronha V, Joshi A, et al. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017;2(1): e000168. [Crossref]  [PubMed]  [PMC] 
  7. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-3334. [Crossref]  [PubMed] 
  8. Li N, Ou W, Yang H, et al. A randomized phase 2 trial of erlotinib versus pemetrexed as second-line therapy in the treatment of patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma. Cancer. 2014;120(9):1379-1386. [Crossref]  [PubMed] 
  9. Han B, Yang L, Wang X, Yao L. Efficacy of pemetrexed-based regimens in advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations after tyrosine kinase inhibitor failure: a systematic review. Onco Targets Ther. April 2018;(11):2121-2129. [Crossref]  [PubMed]  [PMC] 
  10. Lee SJ, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Pemetrexed plus platinum versus pemetrexed alone in non-small cell lung cancer patients who have progressed after first-line EGFR TKIs. Lung Cancer. 2015;90(2):261-266. [Crossref]  [PubMed] 
  11. Park S, Keam B, Kim SH, et al. Pemetrexed singlet versus nonpemetrexed-based platinum doublet as second-line chemotherapy after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor failure in non-small cell lung cancer patients with EGFR mutations. Cancer Res Treat. 2015;47(4): 630-637. [Crossref]  [PubMed]  [PMC] 
  12. Soria JC, Wu YL, Nakagawa K, et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015;16(8): 990-998. [Crossref] 
  13. Yang CJ, Tsai MJ, Hung JY, et al. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment. Onco Targets Ther. March 2016;(9):1579-1587. [Crossref]  [PubMed]  [PMC] 
  14. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-2177. [Crossref]  [PubMed] 
  15. Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917-929. [Crossref] 
  16. Novello S, Mazières J, Oh IJ, et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018;29(6): 1409-1416. [Crossref]  [PubMed]  [PMC] 
  17. Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017;18(7): 874-886. [Crossref] 
  18. Camidge DR, Kono SA, Lu X, et al. Anaplastic lymphoma kinase gene rearrangements in non-small cell lung cancer are associated with prolonged progression-free survival on pemetrexed. J Thorac Oncol. 2011;6(4):774-780. [Crossref]  [PubMed]  [PMC] 
  19. Park S, Park TS, Choi CM, et al. Survival benefit of pemetrexed in lung adenocarcinoma patients with anaplastic lymphoma kinase gene rearrangements. Clin Lung Cancer. 2015;16(5):e83-89. [Crossref]  [PubMed] 
  20. Jo J, Kim SH, Kim YJ, et al. Efficacy of pemetrexed-based chemotherapy in comparison to non-pemetrexed-based chemotherapy in advanced, ALK+ non-small cell lung cancer. Yonsei Med J. 2018;59(2):202-210. [Crossref]  [PubMed]  [PMC] 
  21. Song Z, Su H, Zhang Y. Patients with ROS1 rearrangement-positive non-small-cell lung cancer benefit from pemetrexed-based chemotherapy. Cancer Med. 2016;5(10): 2688-2693. [Crossref]  [PubMed]  [PMC] 
  22. Chen YF, Hsieh MS, Wu SG, et al. Efficacy of pemetrexed-based chemotherapy in patients with ROS1 fusion-positive lung adenocarcinoma compared with in patients harboring other driver mutations in east asian populations. J Thorac Oncol. 2016;11(7):1140-1152. [Crossref]  [PubMed] 
  23. Shaw AT, Varghese AM, Solomon BJ, et al. Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer. Ann Oncol. 2013;24(1):59-66. [Crossref]  [PubMed]  [PMC]