Progression-free survival at 2 years is a reliable surrogate marker for the 5-year survival rate in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy

Hiroaki Akamatsu, Keita Mori, Tateaki Naito, Hisao Imai, Akira Ono, Takehito Shukuya, Tetsuhiko Taira, Hirotsugu Kenmotsu, Haruyasu Murakami, Masahiro Endo, Hideyuki Harada, Toshiaki Takahashi, Nobuyuki Yamamoto, Hiroaki Akamatsu, Keita Mori, Tateaki Naito, Hisao Imai, Akira Ono, Takehito Shukuya, Tetsuhiko Taira, Hirotsugu Kenmotsu, Haruyasu Murakami, Masahiro Endo, Hideyuki Harada, Toshiaki Takahashi, Nobuyuki Yamamoto

Abstract

Background: In locally advanced Non-Small-Cell Lung Cancer (LA-NSCLC) patients treated with chemoradiotherapy (CRT), optimal surrogate endpoint for cure has not been fully investigated.

Methods: The clinical records of LA-NSCLC patients treated with concurrent CRT at Shizuoka Cancer Center between Sep. 2002 and Dec. 2009 were reviewed. The primary outcome of this study was to evaluate the surrogacy of overall response rate (ORR) and progression-free survival (PFS) rate at 3-month intervals (from 9 to 30 months after the initiation of treatment) for the 5-year survival rate. Landmark analyses were performed to assess the association of these outcomes with the 5-year survival rate.

Results: One hundred and fifty-nine patients were eligible for this study. The median follow-up time for censored patients was 57 months. The ORR was 72%, median PFS was 12 months, and median survival time was 39 months.Kaplan-Meier curve of progression-free survival and hazard ratio of landmark analysis at each time point suggest that most progression occurred within 2 years. With regard to 5-year survival rate, patients with complete response, or partial response had a rate of 45%. Five-year survival rates of patients who were progression free at each time point (3-months intervals from 9 to 30 months) were 53%, 69%, 75%, 82%, 84%, 89%, 90%, and 90%, respectively. The rate gradually increased in accordance with progression-free interval extended, and finally reached a plateau at 24 months.

Conclusions: Progression-free survival at 2 years could be a reliable surrogate marker for the 5-year survival rate in LA-NSCLC patients treated with concurrent CRT.

Figures

Figure 1
Figure 1
Kaplan-Meier-estimated PFS (dashed line) and OS curve (bold line) in LA-NSCLC patients treated with concurrent CRT (n = 159).
Figure 2
Figure 2
Hazard ratio of landmark analysis at each time point. Dashed lines indicate 95% confidence intervals. Abbreviations: CR, complete response; PR, partial response.
Figure 3
Figure 3
Five-year survival rates of patients who achieved each outcome. The bars indicate 95% confidence intervals.

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.
    1. Govindan R, Bogart J, Vokes EE. Locally Advanced Non-small Cell Lung Cancer: The Past, Present, and Future. J Thorac Oncol. 2008;3:917–928. doi: 10.1097/JTO.0b013e318180270b.
    1. Reinfuss M, Glinski B, Kowalska T, Kulpa J, Zawila K, Reinfuss K, Dymek P, Herman K, Skolyszewski J. Radiotherapy for stage III, inoperable, asymptomatic small cell lung cancer. Final results of a prospective randomized study (240 patients) Cancer Radiother. 1999;3(6):475–479. doi: 10.1016/S1278-3218(00)88254-2.
    1. Sause W, Kolesar P, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran W Jr, Byhardt R, Dar AR, Turrisi A. Final Results of Phase III Trial in Regionally Advanced Unresectable Non-Small Cell Lung Cancer. Chest. 2000;117:358–364. doi: 10.1378/chest.117.2.358.
    1. Auperin A, Le Pe’choux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non–Small-Cell Lung Cancer. J Clin Oncol. 2010;28:2181–2190. doi: 10.1200/JCO.2009.26.2543.
    1. O’Rourke N, Roqué I, Figuls M, Farré Bernadó N, Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. 2010;16(6):CD002140.
    1. Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non–small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010;28:3739–3745. doi: 10.1200/JCO.2009.24.5050.
    1. Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, Ueoka H, Takemoto M, Kanazawa S, Takata I, Nogami N, Hotta K, Hiraki A, Tabata M, Matsuo K, Tanimoto M. Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010;28:3299–3306. doi: 10.1200/JCO.2009.24.7577.
    1. Ichinose Y, Seto T, Sasaki T, Yamanaka T, Okamoto I, Takeda K, Tanaka M, Katakami N, Sawa T, Kudoh S, Saka H, Nishimura Y, Nakagawa K, Fukuoka M. S-1 plus cisplatin with concurrent radiotherapy for locally advanced non-small cell lung cancer: a multi-institutional phase II trial (West Japan Thoracic Oncology Group 3706) J Thorac Oncol. 2011;6(12):2069–2075. doi: 10.1097/JTO.0b013e3182307e5a.
    1. Sekine I, Noda K, Oshita F, Yamada K, Tanaka M, Yamashita K, Nokihara H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T, Kodama T, Sumi M, Saijo N. Phase I study of cisplatin, vinorelbine, and concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer. Cancer Sci. 2004;95(8):691–695. doi: 10.1111/j.1349-7006.2004.tb03331.x.
    1. Naito Y, Kubota K, Nihei K, Fujii T, Yoh K, Niho S, Goto K, Ohmatsu H, Saijo N, Nishiwaki Y. Concurrent chemoradiotherapy with cisplatin and vinorelbine for stage III non-small cell lung cancer. J Thorac Oncol. 2008;3(6):617–622. doi: 10.1097/JTO.0b013e3181753b38.
    1. Nishimura Y, Harada H, Soejima T, Tsujino K, Hayakawa K, Kozuka T, Tanaka M, Sasaki T, Yamamoto N, Nakagawa K. Phase II study of Nimotuzumab in combination with concurrent chemoradiation therapy (CRT) in patients with locally advanced Non-small Cell Lung Cancer (NSCLC) Int J Radiat Oncol Biol Phys. 2012;84(3):S68.
    1. McAleer MF, Moughan J, Byhardt RW, Cox JD, Sause WT, Komaki R. Does response to induction chemotherapy predict survival for locally advanced non-small cell lung cancer? Secondary analysis of RTOG 8804/8808. Int J Radiat Oncol Biol Phys. 2010;76(3):802–808. doi: 10.1016/j.ijrobp.2009.02.053.
    1. Kim DW, Shyr Y, Shaktour B, Akerley W, Johnson DH, Choy H. Long term follow up and analysis of long term survivors in patients treated with paclitaxel-based concurrent chemo/radiation therapy for locally advanced non-small cell lung cancer. Lung Cancer. 2005;50:235–245. doi: 10.1016/j.lungcan.2005.05.020.
    1. Mauguen A, Pignon JP, Burdett S, Domerg C, Fisher D, Paulus R, Mandrekar SJ, Belani CP, Shepherd FA, Eisen T, Pang H, Collette L, Sause WT, Dahlberg SE, Crawford J, O’Brien M, Schild SE, Parmar M, Tierney JF, Le Pechoux C, Michiels S. Surrogate Lung Project Collaborative Group. Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients’ data. Lancet Oncol. 2013;14(7):619–626. doi: 10.1016/S1470-2045(13)70158-X.
    1. Bradley JD, Paulus R, Komaki R, Masters GA, Forster K, Schild SE, Bogart J, Garces YI, Narayan S, Kavadi V, Nedzi LA, Michalski JM, Johnson D, MacRae RM, Curran WJ, Choy H. A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for stage III non-small cell lung cancer: Results on radiation dose in RTOG 0617. J Clin Oncol. 2013;31(15):7501.

Source: PubMed

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