Advertisement

Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: A multicentre retrospective cohort study

Published:December 02, 2022DOI:https://doi.org/10.1016/j.ejca.2022.10.029

      Highlights

      • Large study of 33 patients with osimertinib continuation or re-administration after pneumonitis.
      • The incidence rate of relapsed pneumonitis was 15%, and all were mild.
      • Osimertinib may be safely and effectively administered after control of initial pneumonitis.

      Abstract

      Introduction

      Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis.

      Methods

      We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge.

      Results

      In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1–21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months – not reached).

      Conclusion

      Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2020.
        CA Cancer J Clin. 2020; 70: 7-30https://doi.org/10.3322/caac.21590
        • Soria J.C.
        • Ohe Y.
        • Vansteenkiste J.
        • Reungwetwattana T.
        • Chewaskulyong B.
        • Lee K.H.
        • et al.
        Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer.
        N Engl J Med. 2018; 378: 113-125https://doi.org/10.1056/NEJMoa1713137
        • Ramalingam S.S.
        • Vansteenkiste J.
        • Planchard D.
        • Cho B.C.
        • Gray J.E.
        • Ohe Y.
        • et al.
        Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC.
        N Engl J Med. 2020; 382: 41-50https://doi.org/10.1056/NEJMoa1913662
        • Hanna N.H.
        • Schneider B.J.
        • Temin S.
        • Baker Jr., S.
        • Brahmer J.
        • Ellis P.M.
        • et al.
        Therapy for Stage IV non-small-cell lung cancer without driver alterations: ASCO and OH (CCO) joint guideline update.
        J Clin Oncol. 2020; 38: 1608-1632https://doi.org/10.1200/JCO.19.03022
        • Suh C.H.
        • Park H.S.
        • Kim K.W.
        • Pyo J.
        • Hatabu H.
        • Nishino M.
        Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: meta-analysis of 153 cohorts with 15,713 patients: meta-analysis of incidence and risk factors of EGFR-TKI pneumonitis in NSCLC.
        Lung Cancer. 2018; 123: 60-69https://doi.org/10.1016/j.lungcan.2018.06.032
        • Ohe Y.
        • Imamura F.
        • Nogami N.
        • Okamoto I.
        • Kurata T.
        • Kato T.
        • et al.
        Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset.
        Jpn J Clin Oncol. 2019; 49: 29-36https://doi.org/10.1093/jjco/hyy179
        • Ahn M.J.
        • Tsai C.M.
        • Shepherd F.A.
        • Bazhenova L.
        • Sequist L.V.
        • Hida T.
        • et al.
        Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: long-term follow-up from a pooled analysis of 2 phase 2 studies.
        Cancer. 2019; 125: 892-901https://doi.org/10.1002/cncr.31891
        • Kenmotsu H.
        • Wakuda K.
        • Mori K.
        • Kato T.
        • Sugawara S.
        • Kirita K.
        • et al.
        Randomized phase 2 study of osimertinib plus bevacizumab versus osimertinib for untreated patients with non-squamous non-small cell lung cancer harboring EGFR mutations; WJOG9717L study.
        J Thorac Oncol. 2022; 17: 1098-1108https://doi.org/10.1016/j.jtho.2022.05.006
      1. Tagrisso: EPAR-Product information. European Medicine Agency, 2016: 50
        • Noonan S.A.
        • Sachs P.B.
        • Camidge D.R.
        Transient asymptomatic pulmonary opacities occurring during osimertinib treatment.
        J Thorac Oncol. 2016; 11: 2253-2258https://doi.org/10.1016/j.jtho.2016.08.144
        • Lee H.
        • Lee H.Y.
        • Sun J.M.
        • Lee S.H.
        • Kim Y.
        • Park S.E.
        • et al.
        Transient asymptomatic pulmonary opacities during osimertinib treatment and its clinical implication.
        J Thorac Oncol. 2018; 13: 1106-1112https://doi.org/10.1016/j.jtho.2018.04.038
        • Kodama H.
        • Wakuda K.
        • Yabe M.
        • Nishioka N.
        • Miyawaki E.
        • Miyawaki T.
        • et al.
        Retrospective analysis of osimertinib re-challenge after osimertinib-induced interstitial lung disease in patients with EGFR-mutant non-small cell lung carcinoma.
        Invest New Drugs. 2021; 39: 571-577https://doi.org/10.1007/s10637-020-01005-1
        • Sato Y.
        • Sumikawa H.
        • Shibaki R.
        • Morimoto T.
        • Sakata Y.
        • Oya Y.
        • et al.
        Drug-related pneumonitis induced by osimertinib as first-line treatment for EGFR-positive non-small cell lung cancer: a real-world setting.
        Chest. 2022; https://doi.org/10.1016/j.chest.2022.05.035
        • Sakata Y.
        • Sakata S.
        • Oya Y.
        • Tamiya M.
        • Suzuki H.
        • Shibaki R.
        • et al.
        Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT).
        Eur J Cancer. 2021; 159: 144-153https://doi.org/10.1016/j.ejca.2021.09.041
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • Schwartz L.H.
        • Sargent D.
        • Ford R.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45 (version 1.1): 228-247https://doi.org/10.1016/j.ejca.2008.10.026
        • USD
        O.H.A.H. SERVICES, common terminology criteria for adverse events (CTCAE).
        (version 5.0)2017: 155
        • NC Institute
        NCI guidelines: Adverse event reporting requirements.
        2012
        • Johkoh T.
        • Lee K.S.
        • Nishino M.
        • Travis W.D.
        • Ryu J.H.
        • Lee H.Y.
        • et al.
        Chest CT Diagnosis and clinical management of drug-related pneumonitis in patients receiving molecular targeting agents and immune checkpoint inhibitors: a position paper from the Fleischner Society.
        Radiology. 2021; 298: 550-566https://doi.org/10.1148/radiol.2021203427
        • Mok T.S.
        • Wu Y.-L.
        • Ahn M.-J.
        • Garassino M.C.
        • Kim H.R.
        • Ramalingam S.S.
        • et al.
        Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer.
        N Engl J Med. 2017; 376: 629-640https://doi.org/10.1056/NEJMoa1612674
        • Baggstrom M.Q.
        • Waqar S.N.
        • Sezhiyan A.K.
        • Gilstrap E.
        • Gao F.
        • Morgensztern D.
        • et al.
        Barriers to enrollment in non-small cell lung cancer therapeutic clinical trials.
        J Thorac Oncol. 2011; 6: 98-102https://doi.org/10.1097/JTO.0b013e3181fb50d8
        • Kawachi H.
        • Fujimoto D.
        • Morimoto T.
        • Ito M.
        • Teraoka S.
        • Sato Y.
        • et al.
        Clinical characteristics and prognosis of patients with advanced non-small-cell lung cancer who are ineligible for clinical trials.
        Clin Lung Cancer. 2018; 19: e721-e734https://doi.org/10.1016/j.cllc.2018.05.014
        • Akamatsu H.
        • Inoue A.
        • Mitsudomi T.
        • Kobayashi K.
        • Nakagawa K.
        • Mori K.
        • et al.
        Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer: combined analysis of two Phase III trials (NEJ 002 and WJTOG 3405).
        Jpn J Clin Oncol. 2013; 43: 664-668https://doi.org/10.1093/jjco/hyt049
        • Lorenzi M.
        • Ferro A.
        • Cecere F.
        • Scattolin D.
        • Del Conte A.
        • Follador A.
        • et al.
        First-line osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: outcome and safety in the real world: FLOWER study.
        Oncologist. 2022; 27: 87-e115https://doi.org/10.1002/onco.13951