Prognostic factors affecting survival in third-line treatment of advanced non-small cell lung cancer: Retrospective cohort study

Abstract

Aim: In patients who have reached third-line treatment, survival times are short and response to treatment is poor. However, in some patients, survival times and treatment responses are good despite advanced treatment lines. The present study investigates the prognostic factors that affect survival among patients who have undergone third-line treatment for non-small cell lung cancer (NSCLC).
Methods: Among the 1,150 patients who were treated for and followed-up with a diagnosis of NSCLC between January 2008 and December 2015, 102 (8%) who had received third-line treatment were included in this retrospective cohort study.
Results: The mean patient age was 56 years (SD: 10.1), and 70.6% were male. The third-line treatment provided a median PFS of 2.36 (range: 1.15–36.1) months and an OS of 4.2 (range: 1.28–38.1) months. Cox hazard-model analyses indicated significant associations between prolonged survival and gender, smoking, non-squamous histology, age below 45 years, the presence of EGFR mutations and the use of EGFR tyrosine kinase inhibitors.
Conclusion: The prognosis may be better for some patients who have reached third-line treatments, namely, young patients, females, non-smokers, and those with a non-squamous histology. In these patients, physicians should be alert in terms of driver mutations, such as EGFR mutation.

Keywords

• Third-line treatment,Anti-EGFR,Treatment,Prognosis,Non-small cell lung cancer

İleri evre küçük hücre dışı akciğer kanserinde üçüncü basamak tedavide sağ kalımı ekileyen prognostik faktörler: Retrospektif kohort çalışma

Abstract

Amaç: Üçüncü basamak tedaviye ulaşmış hastalarda sağkalım süreleri kısa ve tedaviye yanıtları kötüdür. Ancak bazı hastalarda sağkalım süreleri ve tedavi yanıtları ilerlemiş tedavi basamağına rağmen iyidir. Bu çalışmadaki amacımız, küçük hücreli dışı akciğer kanserinde (KHDAK) üçüncü basamak tedaviye ulaşmış olan hastaların sağkalımlarını etkileyen prognostik faktörleri saptamaktır.
Yöntemler: Ocak 2008-Aralık 2015 tarihleri arasında KHDAK tanısı ile tedavi edilen ve takip edilen 1.150 hastadan üçüncü basamak tedavi alan 102 (%8) hasta bu retrospektif kohort çalışmada değerlendirildi.
Bulgular: Hastaların ortalama yaşı 54 (Standard sapma: 10,1) ve %70,6 sı erkekti. Üçüncü basmakta ortanca progresyonsuz sağkalım süresi ortanca 2.36 (Aralık: 1,15-36,1) ve ortanca toplam sağkalım 4.2 (1,28-38,1) aydı. Cox hazard modeli analizinde uzun sağkalımı etkileyen temel faktörler; cinsiyet, sigara, skuamöz dışı histoloji, 45 yaş altında olmak, EGFR mutasyon durumu ve Anti-EGFR tedavi almış olmak olarak saptandı.
Sonuç: Kadın, sigara içmeyen, skuamöz dışı histolojisi olan, genç olan üçüncü basamak tedaviye ulaşmış hastalarda prognozun daha iyi olabileceği ve bu hastalarda EGFR mutasyonu gibi driver mutasyonları açısından hassas olunması gerektiği bilinmelidir.

Keywords

• Üçüncü basamak tedavi,Anti-EGFR,Tedavi,Prognoz,Küçük hücre dışı akciğer kanseri

References

1. 1. Özmen S, Ceylan O. Trends in lung cancer incidence within the last 10 years: An Eastern Anatolian single center experience. J Surg Med. 2020;4(2). Early pub doi: 10.28982/josam.683464
2. 2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29.
3. 3. Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, Penberthy L. Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992-2013. Cancer Epidemiol Biomarkers Prev. 2017 Apr;26(4):632-641. doi: 10.1158/1055-9965.EPI-16-0520.
4. 4. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. (2008). 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 Jul 20;26(21):3543-51.
5. 5. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.
6. 6. Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT, et al. Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol. 2008 Mar 20;26(9):1472-8. doi: 10.1200/JCO.2007.13.0062.
7. 7. Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. doi: 10.1158/2159-8290.CD-14-0326.
8. 8. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497-500.

9. 9. Ramalingam SS, Yang JCH, Lee C, Kurata T, Kim DW, John T, et al. AZD9291 in treatment-naïve EGFRm advanced NSCLC: AURA first-line cohort. In: Journal of Thoracic Oncology, 2015, September, Vol. 10, No. 9, pp. S319-S320.
10. 10. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643.
11. 11. Weiss JM, Stinchcombe TE. Second-Line Therapy for Advanced NSCLC. Oncologist. 2013;18(8):947-53.
12. 12. Langer CJ, Mok T, Postmus PE. Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). Cancer Treat Rev. 2013 May;39(3):252-60.
13. 13. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. doi: 10.1016/S1470-2045(11)70184-X.
14. 14. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. doi: 10.1093/annonc/mdv276.
15. 15. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X.
16. 16. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. doi: 10.1093/annonc/mdv270.
17. 17. Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011 Jul 20;29(21):2866-74. doi: 10.1200/JCO.2010.33.4235.
18. 18. Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, 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 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1.
19. 19. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137.
20. 20. Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He
21. 21. Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-40. doi: 10.1056/NEJMoa1612674.
22. 22. Fiegl M, Hilbe W, Auberger J, Schmid T, Auberger T, Tzankov A, et al. Twelve-year retrospective analysis of lung cancer-The TYROL Study: Daily routine in 1,424 patients (1995-2006). J Clin Oncol. 2008;26:19063.
23. 23. Kaira K, Takahashi T, Murakami H, Tsuya A, Nakamura Y, Naito T, et al. Long-term survivors of more than 5 years in advanced non-small cell lung cancer. Lung Cancer. 2010;67(1):120-3.
24. 24. Kawaguchi T, Takada M, Kubo A, Matsumura A, Fukai S, Tamura A, et al. Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol. 2010 May;5(5):620-30. doi: 10.1097/JTO.0b013e3181d2dcd9.
25. 25. Ying Geng Z, Chang Jiao S, Cui Liu S, Li Y, Feng Liu Z, Qing Zhang G, Jie Wang L, et al. Third-line therapy in advanced non-small cell lung cancer. J BUON. 2013 Oct-Dec;18(4):899-907.
26. 26. Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, et al. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. doi: 10.1200/JCO.2013.52.4694.
27. 27. Zhao D, Chen X, Qin N, Su D, Zhou L, Zhang Q, et al. The prognostic role of EGFR-TKIs for patients with advanced non-small cell lung cancer. Scientific Reports 2017;7:40374.