Clinical outcomes, local–regional control and the role for metastasis-directed therapies in stage III non-small cell lung cancers treated with chemoradiation and durvalumab Journal Article


Authors: Offin, M.; Shaverdian, N.; Rimner, A.; Lobaugh, S.; Shepherd, A. F.; Simone, C. B. 2nd; Gelblum, D. Y.; Wu, A. J.; Lee, N.; Kris, M. G.; Rudin, C. M.; Zhang, Z.; Hellmann, M. D.; Chaft, J. E.; Gomez, D. R.
Article Title: Clinical outcomes, local–regional control and the role for metastasis-directed therapies in stage III non-small cell lung cancers treated with chemoradiation and durvalumab
Abstract: Background and purpose: Concurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined. Materials and methods: We reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local–regional and metastatic failures. Results: Sixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51–79%) and 85% (95% CI: 75–95%), respectively. The cumulative 12-month incidence of local–regional and distant failures were 18% (95% CI: 5.9–30%) and 30% (95% CI: 16.3–44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS. Conclusions: Outcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone. © 2020 Elsevier B.V.
Keywords: controlled study; aged; treatment failure; gene mutation; major clinical study; overall survival; cisplatin; cancer growth; drug withdrawal; treatment duration; paclitaxel; cancer staging; drug megadose; follow up; cancer incidence; carboplatin; progression free survival; multiple cycle treatment; etoposide; neuropathy; cytotoxicity; distant metastasis; arthralgia; pneumonia; rash; corticosteroid; pemetrexed; disease exacerbation; chemoradiotherapy; non small cell lung cancer; concurrent chemoradiation; myositis; clinical outcome; oncological parameters; non-small cell; disease burden; human; male; female; priority journal; article; durvalumab; local-regional control; metastasis-directed therapies; local regional control
Journal Title: Radiotherapy and Oncology
Volume: 149
ISSN: 0167-8140
Publisher: Elsevier Inc.  
Date Published: 2020-08-01
Start Page: 205
End Page: 211
Language: English
DOI: 10.1016/j.radonc.2020.04.047
PROVIDER: scopus
PUBMED: 32361014
PMCID: PMC8239428
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Zhigang Zhang
    427 Zhang
  2. Daphna Y Gelblum
    227 Gelblum
  3. Daniel R Gomez
    237 Gomez
  4. Nancy Y. Lee
    871 Lee
  5. Jamie Erin Chaft
    289 Chaft
  6. Andreas Rimner
    524 Rimner
  7. Abraham Jing-Ching Wu
    400 Wu
  8. Mark Kris
    869 Kris
  9. Matthew David Hellmann
    411 Hellmann
  10. Charles Rudin
    488 Rudin
  11. Michael David Offin
    170 Offin
  12. Annemarie Fernandes Shepherd
    103 Shepherd
  13. Charles Brian Simone
    190 Simone
  14. Stephanie Marie Lobaugh
    56 Lobaugh