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.
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.
['Offin|Michael|M|', 'Shaverdian|Narek|N|', 'Rimner|Andreas|A|', 'Lobaugh|Stephanie|S|', 'Shepherd|Annemarie F|AF|', 'Simone|Charles B|CB|', 'Gelblum|Daphna Y|DY|', 'Wu|Abraham J|AJ|', 'Lee|Nancy|N|', 'Kris|Mark G|MG|', 'Rudin|Charles M|CM|', 'Zhang|Zhigang|Z|', 'Hellmann|Matthew D|MD|', 'Chaft|Jamie E|JE|', 'Gomez|Daniel R|DR|']
D000368:Aged D000911:Antibodies, Monoclonal D002289:Carcinoma, Non-Small-Cell Lung D059248:Chemoradiotherapy D006801:Humans D008175:Lung Neoplasms
Local-regional control Metastasis-directed therapies Non-small cell Durvalumab Concurrent chemoradiation