The Impact of Durvalumab on Local Regional Control in Stage III Non-Small Cell Lung Cancers Treated with Chemoradiation and on KEAP1/NFE2L2 Mutant Tumors

Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. Results Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. Conclusion hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

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The impact of the new TNM classification on survival of patients in stage III non-small cell lung cancer

Annals of Oncology ◽

10.1093/annonc/mdy291.003 ◽

2018 ◽

Vol 29 ◽

pp. viii489

Author(s):

M. Vrankar ◽

K. Stanic

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tnm Classification ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

The Impact

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Locoregional control, failure patterns and clinical outcomes in patients with stage III non-small cell lung cancers treated with chemoradiation and durvalumab.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21058 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21058-e21058

Author(s):

Michael Offin ◽

Narek Shaverdian ◽

Andreas Rimner ◽

Stephanie Lobaugh ◽

Annemarie Shepherd ◽

...

Keyword(s):

Disease Progression ◽

Progression Free Survival ◽

Small Cell ◽

Stage Iii ◽

Metastatic Progression ◽

Disease Relapse ◽

Small Cell Lung ◽

Lung Cancers ◽

Failure Patterns ◽

Ablative Therapies

e21058 Background: Definitive concurrent chemoradiation (cCRT) and durvalumab is a 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 to date remain undefined. Methods: We reviewed patients with stage III unresectable NSCLC treated between November 2017 and February 2019 with cCRT. Patients that received at least one cycle of durvalumab were further assessed for 12-month progression free survival (PFS), overall survival (OS), and the incidence and pattern of local-regional and metastatic failures. Disease-relapse was characterized to determine patients potentially eligible for metastasis-directed ablative therapies. Toxicities leading to durvalumab discontinuation were evaluated using CTCAE v.5.0. Results: Of the 83 patients with stage III NSCLC treated with cCRT (median 60Gy), 62 received durvalumab and were evaluable (median follow-up: 12 months). Patients (n = 21, 25%) did not receive durvalumab largely related to metastatic progression (n = 9) or persistent cCRT toxicity (n = 10). In the 62 durvalumab treated patients the median age was 66 (range: 49 - 86), 73% had stage IIIB (n = 33) or IIIC (n = 12) disease, and 58% (n = 36) had adenocarcinoma. The median time from cCRT end to durvalumab start was 1.5 months. Patients received a median of 8 months of durvalumab; 35% (n = 22) of patients completed 12 months of therapy. Common reasons for discontinuing 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. High TMB (≥ 8.8 mt/Mb) or PD-L1 (≥ 1% or PD-L1 ≥ 50%) did not predict improved PFS. Patients who discontinued durvalumab due to toxicity did not have inferior PFS. The cumulative 12-month incidence of local-regional and distant metastatic failures were 18% (95% CI: 5.9 - 30%) and 30% (95% CI: 16.3 - 44.5%), respectively. Of the 17 patients with distant metastases, 9 had oligometastases and would have been potential candidates for comprehensive ablative therapies. Conclusions: Outcomes and toxicities outcomes with cCRT and durvalumab in clinical practice align with the PACIFIC trial. Analysis of disease-relapse suggests a substantial minority of patients with disease progression may be potential candidates for metastasis-directed therapies. Local regional outcomes appear improved to historical data of cCRT alone.

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