79MO PACIFIC-R: Real-world characteristics of unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy

9054 Background: In the phase 3 PACIFIC trial of unresectable, stage III NSCLC patients (pts) without progression after concurrent chemoradiotherapy (cCRT), durvalumab (durva) significantly improved PFS and OS with similar safety compared to placebo (pbo). We performed exploratory analyses to characterize first subsequent treatment (Tx) after discontinuation of durva. Methods: Pts with WHO PS 0/1 and any tumor PD-L1 status were randomized (2:1) 1–42 days after ≥2 cycles of platinum-based cCRT to durva 10 mg/kg IV or pbo Q2W up to 12 months, stratified by age, sex and smoking history. Pts were classified by the use or not of first subsequent Tx and category of first systemic Tx (platinum doublet CT [PDCT], single-agent CT [SCT], immunotherapy [IT] or targeted therapy [TT]). Results: As of Mar 22, 2018, 216/476 (45.4%) and 153/237 (64.6%) in the durva and pbo arms, respectively, had a RECIST-based PFS event per BICR (5.7% and 8.4% due to death). 195 (41.0%) and 128 (54.0%) received first subsequent Tx, most of which were systemic Tx (158 [33.2%] and 109 [46.0%]): PDCT (16.4% and 19.0%), SCT (8.6% and 8.4%), IT (4.2% and 13.5%) or TT (3.8% and 5.1%); 7.8% and 8.0% received RT only. Time to first subsequent therapy or death (TFST) was longer with durva vs pbo (HR 0.58; 95% CI 0.47–0.72; median 21.0 vs 10.4 months). Baseline characteristics of pts with or without first subsequent Tx were similar, and similar across durva or pbo arms. Among pts with systemic Tx, baseline characteristics (including pre-cCRT PD-L1 status) were generally similar, except pts on TT, more of whom were EGFR+ (70.0% vs 0–6.6% of other systemic Tx groups) with commonly associated phenotypes (more females, Asians, non-smokers and non-squamous pts). Best overall response to first systemic Tx will be presented. Conclusions: Due to longer PFS and fewer progression events with durva vs pbo, fewer pts on durva required subsequent Tx and, per TFST, much later. With the exception of IT, use of each subsequent Tx was similar between the durva and pbo arms with PDCT the most common. Baseline characteristics were similar for pts with or without first subsequent Tx and pts who received first systemic Tx, except for pts who received TT, as expected due to their molecular profile.

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PCN44 Cost-Effectiveness of Durvalumab Following Chemoradiotherapy in Unresectable Stage III NSCLC Patients in the US: An Update Based on 4-Year Survival Data

Value in Health ◽

10.1016/j.jval.2021.04.136 ◽

2021 ◽

Vol 24 ◽

pp. S26-S27

Author(s):

B. Seal ◽

M.J. Mooradian ◽

M. Van Keep ◽

W. Dunlop ◽

L. Brannman ◽

...

Keyword(s):

Cost Effectiveness ◽

Survival Data ◽

Stage Iii ◽

Unresectable Stage ◽

The Us ◽

Stage Iii Nsclc ◽

Nsclc Patients

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Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e20532 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e20532-e20532

Author(s):

Christine Pierce ◽

Yuting Kuang ◽

Hsiu-Ching Chang ◽

Arianna Nevo ◽

Anne Deitz ◽

...

Keyword(s):

Observational Studies ◽

Meta Analysis ◽

Stage Iii ◽

Baseline Risk ◽

Small Cell Lung ◽

Unresectable Stage ◽

Immune Mediated ◽

Stage Iii Nsclc ◽

Grade 3 ◽

Nsclc Patients

e20532 Background: Recent clinical trials have shown positive results for therapies combining concurrent chemoradiation therapy (cCRT) and checkpoint immunotherapy in unresectable non-small cell lung cancer (NSCLC). cCRT is associated with an increased risk of pneumonitis, a severe and life-threatening inflammation of the lungs. To further inform clinical decision-making and support the evaluation of new therapies combining immunotherapies with cCRT, it is important to understand the baseline risk of pneumonitis associated with cCRT alone. The objective of this study was to quantify the incidence of cCRT-induced grade 3−5 pneumonitis (immune-mediated and radiation pneumonitis) in unresectable stage III NSCLC patients. Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to April 24, 2020. Chemotherapies of interest were cisplatin, pemetrexed, etoposide, carboplatin, and paclitaxel. Randomized controlled trials (RCTs), observational studies, and non-randomized trials were included. Bayesian meta-analysis using a binomial model random effects model was conducted with SAS 9.4. Results: Among 1,889 records identified from the search, 17 studies (6 RCTs, 8 observational studies, 3 single-arm trials) met inclusion criteria. Eleven studies were included in the meta-analysis (5 RCTs, 6 observational studies; 1,788 patients). All studies specified radiation-related pneumonitis (RP), although this is clinically indistinguishable from immune-mediated pneumonitis. Patient populations were comparable across studies; the most common chemotherapies were paclitaxel + carboplatin (n = 6) and pemetrexed + cisplatin (n = 5), and radiation doses ranged from 60–74 Gy. There was variation across studies in intervention, outcome reporting, and follow-up (median range: 12–73 months), but this variation was considered acceptable based on sensitivity analyses. The estimated pooled incidence of grade 3−5 RP in cCRT-treated unresectable stage III NSCLC patients was 3.62% [95% confidence interval (CI): 1.65−6.21] in RCTs and 5.98% [95% CI: 2.26−12.91] in observational studies. The pooled incidence of fatal (grade 5) RP was 0.37% [95% CI: 0−2.78] in RCTs and 1.73% [95% CI: 0.53−4.33] in observational studies. Conclusions: This study estimates that 3.62–5.98% of patients with unresectable stage III NSCLC develop grade 3−5 RP when treated with cCRT, with incidence varying by study design. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.

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Oncologist decision drivers in stage III non-small cell lung cancer: Outcomes of a web-based survey.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.27_suppl.35 ◽

2019 ◽

Vol 37 (27_suppl) ◽

pp. 35-35

Author(s):

Adam Yagui-Beltran ◽

Kellie Ryan ◽

Marnie L. Boron ◽

Ion Cotarla ◽

Daryl S. Spinner ◽

...

Keyword(s):

Lung Cancer ◽

Treatment Decision ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Web Based ◽

Unresectable Stage ◽

Stage Iii Nsclc ◽

Nsclc Patients ◽

To Receive

35 Background: Clinical guidelines seek to optimize patient care. We investigated how oncologists manage stage III non-small cell lung cancer (NSCLC) patients from diagnosis through treatment decision-making and drivers impacting guideline adherence. Methods: A sample of US medical oncologists (n=150) participated in a 38-question, 25-min web-based quantitative survey in January 2019. Participation required at least 3 yrs in practice and 3 stage III NSCLC patients treated in the prior 6-mo period. Results: Surveyed oncologists (82% community; 18% academic), on average, had 15 yrs of clinical experience and treated 20 stage III NSCLC patients in the prior 6 mos. Time from first treatment decision to initiation averaged >2–4 wks in 31% and >4 wks in 20% of patients, respectively. Oncologists recommend definitive concurrent chemoradiation therapy (cCRT) in 48% of unresectable stage III NSCLC patients. Reasons for not recommending cCRT include patient unlikely to tolerate cCRT (64% of oncologists), presence of a targetable mutation (41%), patient inability to travel consistently to receive treatment/inconvenient dosing (41%), and patient cost/affordability (34%). Eighteen percent of unresectable stage III NSCLC patients decline recommended cCRT. Fifty-five percent of patients who receive cCRT go on to receive consolidation immunotherapy (IO). Insurance challenges led to oncologists not recommending consolidation IO in 19% of patients. In the 85% of oncologists who conduct EGFR or PD-L1 testing, positive EGFR or negative PD-L1 tests are reasons for not recommending consolidation IO in 27% of patients (12% and 15%, respectively). Over half (55%) of unresectable stage III NSCLC patients who receive definitive cCRT also receive consolidation chemotherapy, which is no longer recommended in guidelines. Patients receiving consolidation CT were less likely to receive consolidation IO than the overall cohort of patients receiving cCRT (42% vs. 55%). Conclusions: Oncologists reported important variances in guidelines and standards of care related to the stage III NSCLC patient treatment journey. While some deviations from both are expected, there may be areas of focus for quality improvement initiatives.

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P2.16-12 Treatment Uptake and Outcomes of Elderly Stage III NSCLC Patients: A 15-Year Retrospective Real-World Study

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1879 ◽

2019 ◽

Vol 14 (10) ◽

pp. S869-S870

Author(s):

A. Gibson ◽

A. D’silva ◽

M. Dean ◽

R. Tudor ◽

A. Elegbede ◽

...

Keyword(s):

Real World ◽

Stage Iii ◽

Treatment Uptake ◽

Stage Iii Nsclc ◽

Nsclc Patients

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Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

Radiation Oncology ◽

10.1186/s13014-020-01696-z ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Martina Vrankar ◽

Izidor Kern ◽

Karmen Stanic

Keyword(s):

Prognostic Value ◽

Performance Status ◽

Immune Checkpoint Blockade ◽

National Registry ◽

Stage Iii ◽

Clinicopathological Parameters ◽

Unresectable Stage ◽

Total Radiation Dose ◽

Stage Iii Nsclc ◽

Nsclc Patients

Abstract Background Expression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC. Methods National registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining. Results Eighty patients (68.4%) expressed PD-L1 of ≥ 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression ≥ 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression ≥ % (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (≥ 50%) with 29.8 months compared to 29.9 months in those with low (1–49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005). Conclusions In our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.

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