Ineligibility for the PACIFIC trial in unresectable stage III non-small cell lung cancer patients

  • Kazutaka Hosoya
  • Daichi FujimotoEmail author
  • Hayato Kawachi
  • Yuki Sato
  • Mariko Kogo
  • Kazuma Nagata
  • Atsushi Nakagawa
  • Ryo Tachikawa
  • Shinya Hiraoka
  • Masaki Kokubo
  • Keisuke Tomii
Original Article



Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible after CRT in the real world. No study has been conducted on the patients who were ineligible for the PACIFIC trial, and hence, we conducted a retrospective study on them.


We identified 82 patients with stage III NSCLC who received definitive platinum-based concurrent CRT and had World Health Organization performance status of 0–1. We investigated the proportion, clinical characteristics, and prognoses of patients who became ineligible for the PACIFIC trial after CRT.


After CRT, 19 of 82 patients (23%) became ineligible for the PACIFIC trial. Comparison between eligible and ineligible patients revealed that old age (p = 0.042), male gender (p = 0.031), and radiation therapy with V20 ≥ 35% (p = 0.032) were associated with ineligibility after CRT. Moreover, ineligible patients showed shorter PFS (6.6 vs. 15.7 months, hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.16–5.89, p = 0.016) and shorter OS (18.6 vs. 44.3 months, HR 3.03, 95% CI 1.29–7.10, p = 0.007) than eligible patients.


Our study revealed the clinical characteristics and prognoses of patients who became ineligible for the PACIFIC trial after CRT. Physicians should be careful while prescribing CRT for patients with characteristics such as old age, male gender, and radiation therapy with V20 ≥ 35%.


Non-small cell lung cancer Definitive chemoradiotherapy Durvalumab Eligibility criteria Outcome 



The authors thank Keiko Sakuragawa for her administrative assistance.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

Dr. Hosoya, Dr. Fujimoto, Dr. Kogo, Dr. Kokubo and Dr. Tomii received lecture fees from AstraZeneca K.K. (Tokyo, Japan). Dr. Fujimoto and Dr. Kogo received research funding from AstraZeneca K.K. (Tokyo, Japan) for separate studies. All remaining authors have no conflicts of interest to declare.

Ethical approval

All study procedures complied with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.


  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30. CrossRefGoogle Scholar
  2. 2.
    Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 62:220–241. CrossRefGoogle Scholar
  3. 3.
    Morgensztern D, Ng S, Gao F, Govindan R (2010) Trends in stage distribution for patients with non-small cell lung cancer: a National Cancer Database survey. J Thorac Oncol 5:29–33CrossRefGoogle Scholar
  4. 4.
    Yoon SM, Shaikh T, Hallman M (2017) Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol 8:1–20. CrossRefGoogle Scholar
  5. 5.
    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC (2017) Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 377:1919–1929. CrossRefGoogle Scholar
  6. 6.
    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC (2018) Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. Google Scholar
  7. 7.
    Vardy J, Dadasovich R, Beale P, Boyer M, Clarke SJ (2009) Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials. BMC Cancer 9:130CrossRefGoogle Scholar
  8. 8.
    Baggstrom MQ, Waqar SN, Sezhiyan AK, Gilstrap E, Gao F, Morgensztern D, Govindan R (2011) Barriers to enrollment in non-small cell lung cancer therapeutic clinical trials. J Thorac Oncol 6:98–102CrossRefGoogle Scholar
  9. 9.
    Al-Baimani K, Jonker H, Zhang T, Goss GD, Laurie SA, Nicholas G, Wheatley-Price P (2018) Are clinical trial eligibility criteria an accurate reflection of a real-world population of advanced non-small-cell lung cancer patients? Curr Oncol 25:e291CrossRefGoogle Scholar
  10. 10.
    Kawachi H, Fujimoto D, Morimoto T, Ito M, Teraoka S, Sato Y, Nagata K, Nakagawa A, Otsuka K, Tomii K (2018) Clinical characteristics and prognosis of patients with advanced non-small cell lung cancer who are ineligible for clinical trials. Clin Lung Cancer. Google Scholar
  11. 11.
    Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T (2010) 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 28:3739–3745. CrossRefGoogle Scholar
  12. 12.
    Carter DL, Garfield D, Hathorn J, Mundis R, Boehm KA, Ilegbodu D, Asmar L, Reynolds C (2012) A randomized phase III trial of combined paclitaxel, carboplatin, and radiation therapy followed by weekly paclitaxel or observation for patients with locally advanced inoperable non-small-cell lung cancer. Clin Lung Cancer 13:205–213. CrossRefGoogle Scholar
  13. 13.
    Senan S, Brade A, Wang LH, Vansteenkiste J, Dakhil S, Biesma B, Martinez Aguillo M, Aerts J, Govindan R, Rubio-Viqueira B, Lewanski C (2016) PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 34:953–962. CrossRefGoogle Scholar
  14. 14.
    Steuer CE, Behera M, Ernani V, Higgins KA, Saba NF, Shin DM, Pakkala S, Pillai RN, Owonikoko TK, Curran WJ, Belani CP (2017) Comparison of concurrent use of thoracic radiation with either carboplatin–paclitaxel or cisplatin–etoposide for patients with stage III non-small-cell lung cancer. JAMA Oncol 3:1120. CrossRefGoogle Scholar
  15. 15.
    Bowden JCS, Williams LJ, Simms A, Price A, Campbell S, Fallon MT, Fearon KCH (2017) Prediction of 90 day and overall survival after chemoradiotherapy for lung cancer: role of performance status and body composition. Clin Oncol 29:576–584. CrossRefGoogle Scholar
  16. 16.
    Sanders K, Hendriks LE, Troost E, Bootsma GP, Houben R, Schols A, Dingemans AMC (2016) Early weight loss during chemoradiotherapy has a detrimental impact on outcome in NSCLC. J Thorac Oncol 11:873–879. CrossRefGoogle Scholar
  17. 17.
    Topkan E, Parlak C, Selek U (2013) Impact of weight change during the course of concurrent chemoradiation therapy on outcomes in stage IIIB non-small cell lung cancer patients: retrospective analysis of 425 patients. Int J Radiat Oncol Biol Phys 87:697–704CrossRefGoogle Scholar
  18. 18.
    Deek MP, Kim S, Ahmed I, Fang BS, Zou W, Malhotra J, Aisner J, Jabbour SK (2016) Prognostic impact of missed chemotherapy doses during chemoradiation therapy for non-small cell lung cancer. Am J Clin Oncol. Google Scholar
  19. 19.
    Shi A, Zhu G, Wu H, Yu R, Li F, Xu B (2010) Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy. Radiat Oncol 5:35. CrossRefGoogle Scholar
  20. 20.
    Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, Bradley JD, Kim TH, Ramella S, Marks LB, De Petris L (2013) Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 85:444–450. CrossRefGoogle Scholar
  21. 21.
    Zhao Y, Chen L, Zhang S, Wu Q, Jiang X, Zhu H, Wang J, Li Z, Xu Y, Zhang YJ, Bai S (2015) Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer. Thorac Cancer 6:49–57. CrossRefGoogle Scholar
  22. 22.
    National Comprehensive Cancer Network (2019) Non-small cell lung cancer (Version 3.2019). Accessed 16 Feb 2019

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Kazutaka Hosoya
    • 1
  • Daichi Fujimoto
    • 1
    Email author
  • Hayato Kawachi
    • 1
  • Yuki Sato
    • 1
  • Mariko Kogo
    • 1
  • Kazuma Nagata
    • 1
  • Atsushi Nakagawa
    • 1
  • Ryo Tachikawa
    • 1
  • Shinya Hiraoka
    • 2
  • Masaki Kokubo
    • 2
  • Keisuke Tomii
    • 1
  1. 1.Department of Respiratory MedicineKobe City Medical Center General HospitalKobeJapan
  2. 2.Department of Radiation OncologyKobe City Medical Center General HospitalKobeJapan

Personalised recommendations