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.

Keywords: Concurrent chemoradiation; Durvalumab; Local-regional control; Metastasis-directed therapies; Non-small cell.

Figure 1.

Outcomes and failures in patients treated with concurrent chemoradiation and durvalumab. (A) Progression-free survival and overall survival, and (B) incidence of local-regional and distant failure as calculated from durvalumab initiation. The 12-month PFS was 65% (95% CI: 51–79%) and the 12-month OS was 85% (95% CI: 75–95%). In blue, the respective 12-month PFS and OS estimates and 95% CI of patients treated in the PACIFIC study is shown (1). The numbers of patients at risk are noted above the x-axis in the survival curves. Shading represents that 95% confidence intervals.

Figure 2.

Representative local-regional disease failure patterns: A) in-field progression of primary tumor within 90% dose volume B) marginal progression of supraclavicular adenopathy adjacent to 50% dose volume C) out-of-field progression of subaortic adenopathy outside 50% dose volume. The 50% radiation dose volume (blue) and 90% dose volume (red) are shown.