Concurrent and sequential chemoradiation therapy are associated with improved survival among unresected stage III non-small cell lung cancer patients in the United States.

7043 Background: Concurrent chemoradiation therapy (cCRT) has been shown to improve survival outcomes among inoperable stage III non-small cell lung cancer (NSCLC) patients compared to sequential CRT (sCRT) and single-modality therapy in clinical trials. However, many “real world” patients do not receive CRT, and less is known about the survival benefits of concurrent CRT vs other treatment modalities in pragmatic, non-clinical trial settings. Methods: We used the National Cancer Database (2004-2011) to identify unresected stage III NSCLC patients (ages 18-79 years) with Charlson comorbidity score ≤1 and 5-year follow up through the end of 2016. cCRT was defined as the initiations of chemotherapy (CT) and radiation therapy (RT) that were ≤14 days (n = 30,290) apart, whereas sCRT was defined as > 14 days apart (total n = 10,596). The remaining three treatment groups included CT only (n = 11,216), RT only (n = 7,772), and neither CT/RT during first course treatment (n = 10,694). Cox proportional hazard model was used to examine the 5-year survival by treatment modalities, controlling for patient demographics, comorbidity score, health insurance, facility type, area-level social deprivation index (SDI, a composite measure for area-level socio-economic status), driving time to the treatment facility, diagnosis year, and region. Adjusted hazard ratios (HR), and medium survivals were generated by treatment modalities. Results: Among 70,568 unresected stage III NSCLC patients, 61,487 (87.1%) patients died within the 5-year follow-up period. In adjusted analyses, cCRT and sCRT had similar survival (median survivals: 15.3 months), whereas other treatment modalities were associated with worse survival compared to cCRT: CT only (median survival: 10.8 months; HR [95%CI]: 1.46 [1.43-1.50]), RT only (median survival: 6.7 months; HR [95%CI]: 1.93[1.88-1.99]), and no treatment (median survival: 3.2 months; HR [95%CI]: 2.64 [2.58-2.71]), all p < 0.001. Higher comorbidity score (Charlson score 1 vs 0, HR [95%CI]: 1.18 [1.16-1.21]), non-private insurance (Medicaid: 1.16 [1.12-1.20]; Medicare: 1.10 [1.08-1.13]; uninsured: 1.21 [1.16-1.26]) were all associated with worse survival (all p < 0.001). Conclusions: Concurrent CRT and sequential CRT have similar survival outcomes among unresected stage III NSCLC patients with minimum comorbidities, however, single modality and no therapy are associated with much poorer survival among “real world” patients, and should be avoided unless clinically appropriate.

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Development of brain metastases in stage III/IV non-small cell lung cancer patients treated with or without erlotinib.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19011 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19011-e19011 ◽

Cited By ~ 1

Author(s):

Jing Liu ◽

Li Kong ◽

Xue Meng ◽

Jinbo Yue ◽

Xindong Sun ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Small Cell ◽

Stage Iii ◽

Control Group ◽

Small Cell Lung ◽

Nsclc Patients ◽

And Control

e19011 Background: Non-small cell lung cancer (NSCLC) has a risk of death from brain metastases (BM) that exceeds potential mortality from extracranial disease progression. Erlotinib has been proved to be effective for NSCLC patients. We hold a study to evaluate value of erlotinib in preventing BM in stage III/IV NSCLC patients. Methods: Pathologically confirmed NSCLC stage III/IV patients were included and divided into erlotinib group and control group according to whether erlotinib administration (at least one month) in 1- or 2-line therapy or not. Stage IV patients with BM were excluded. Patients with any EGFR-TKI treatment were excluded from control group. Times of erlotinib administration to BM and to death or last follow-up were recorded for erlotinib group. Times of corresponding 1- or 2-line chemotherapy to BM and to death or last follow-up were recorded for control group correspondingly. Time to BM, 1- and 2-year incidence of BM were end points. Results: 140 patients were included (68 in erlotinib group and 72 in control group) and all clinical characteristics between two groups were balanced. At a median follow-up of 20.0 months, the median time to BM for all patients was 28.0 months (95% CI, 23.795-32.205 months). 1- and 2-year incidence of BM were 17.8% (95% CI, 10.744-24.856%) and 38.8% (95% CI, 27.236-50.364%) respectively. The median time to BM were 42.0 months (95% CI, 15.567-68.433 months) and 19.0 months (95% CI, 11.305-26.695 months) (P=0.028) for erlotinib group and control group. Erilotinib group has a lower BM incidence than control group (1-year: 14.4%, 95% CI: 4.992%-23.808%, vs 21.1%, 95% CI: 10.712%-31.488%, P=0.384; 2-year: 26.2%, 95% CI: 18.712%-33.688%, vs 50.2%, 95% CI: 34.128%-66.272%, P=0.005). Multivariate analysis shows interval to BM were longer for erlotinib group (HR, 2.531; 95% CI, 1.272-5.051; P=0.008) and stage III disease (HR, 2.093; 95% CI, 1.035-4.231; P=0.040). Conclusions: Erlotinib administration improves time to BM and 2-year incidence of BM of stage III/IV NSCLC patients. Erlotinib administration and stage III disease predicts lower incidence of BM in all patients.

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Actionable policy barriers for receiving standard of care treatment among unresected stage III non-small cell lung cancer (NSCLC) patients in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.2069 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 2069-2069

Author(s):

Zhiyuan Zheng ◽

Charles B. Simone ◽

Stephen G. Chun ◽

Xuesong Han ◽

Helmneh M. Sineshaw ◽

...

Keyword(s):

Lung Cancer ◽

Standard Of Care ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Comorbidity Score ◽

Driving Time ◽

Charlson Comorbidity Score ◽

Standard Of Care Treatment ◽

Nsclc Patients

2069 Background: Recent data suggests that a significant number of good performance, unresectable stage III non-small cell lung cancer (NSCLC) patients do not receive standard-of-care treatment, i.e. concurrent chemoradiotherapy (cCRT) followed by durvalumab, despite being eligible. However, little is known about actionable policy barriers to delivery of cCRT to this patient population. Methods: The National Cancer Database (2004-2016) was used to identify unresected stage III NSCLC patients aged 18-79 years with Charlson comorbidity score ≤ 1. cCRT was defined as the initiations of chemotherapy (CT) and radiation therapy (RT) that were ≤14 days (n = 53,444) apart. The remaining treatment groups included sequential CRT (sCRT; n = 16,666), CT only (n = 15,416), RT only (n = 11,579), and no first course treatment (n = 16,691). Multinomial logistic regressions were used to examine the likelihoods of receiving different treatment modalities, controlling for patient demographics, Charlson comorbidity score, health insurance, facility type, social deprivation index (SDI, a comprehensive socio-economic measure; higher SDI indicates lower socioeconomic status [SES]), driving time to facility, diagnosis year, and region. Results: Of the total 113,796 patients assessed (median age 66 years), most were male (55.7%), non-Hispanic white (81.7%), and with SDI score ≥50 (51.3%). 29.5% had Charlson comorbidity score = 1 while the rest had 0. In adjusted analyses (predicted margins), 47.0% patients received cCRT (sCRT: 14.6%; CT only: 13.5%; RT only: 10.2%; no treatment: 14.7%). Compared to the privately insured, Medicaid, Medicare, and uninsured patients were more likely to receive RT only (relative risk ratios [95%CI]: 1.93 [1.77-2.11]; 1.51 [1.41-1.61]; 1.80 [1.61-2.01], respectively) and no treatment (1.84 [1.71-1.99]; 1.54 [1.45-1.63]; 2.19 [2.01-2.40], respectively) rather than cCRT (all p < .001). Moreover, higher SDI was associated with higher likelihood of receiving RT only (highest vs lowest SDI scores: 1.42 [1.33-1.52]), or no treatment (1.46 [1.38-1.55]) rather than cCRT (all p < .001). Longer driving time was associated with higher likelihood of receiving CT only ( > 120 mins vs < 30 mins: 1.24 [1.10-1.39]), or no treatment (1.33 [1.18-1.50]) rather than cCRT (all p < .001). Conclusions: Health policies should focus on patients who are not privately insured and live in neighborhoods with low SES. Moreover, helping their transportation needs may also improve the likelihood of receiving cCRT.

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Long-term survival trends in patients with unresectable stage III non-small cell lung cancer receiving chemotherapy and radiation therapy: a SEER cancer registry analysis

10.21203/rs.2.15412/v3 ◽

2020 ◽

Author(s):

Ryan N Hansen ◽

Yiduo Zhang ◽

Brian Seal ◽

Kellie Ryan ◽

Candice Yong ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Registry ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Unresectable Stage ◽

Stage Iii Nsclc ◽

Over Time

Abstract Background: To evaluate the value of new therapies for non-small cell lung cancer (NSCLC), it is necessary to understand overall survival (OS) rates associated with previous standard therapies and how these rates have evolved over time. Methods: We retrospectively analyzed data from patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Adults with unresectable, stage III NSCLC treated with chemoradiotherapy were grouped by diagnosis year (2000–2002; 2003–2005; 2006–2008; 2009–2011; 2012–2013). The primary endpoint was OS (data cut-off, December 31, 2014), estimated using the Kaplan–Meier estimator. Temporal survival-trend significance was tested using a two-sided log-rank trend test. Results: Of 12,865 eligible patients, 59.1% were male, 59.9% had stage IIIB disease, and 62.7% had non-squamous histology. Median age at diagnosis was 67 years. Overall, 10,899 (84.7%) patients died and 1,966 (15.3%) were censored/lost to follow-up. Median follow-up (95% confidence interval [CI]) was 80 (77–82) months; median OS (95% CI) was 15 (15–16) months; 1- and 3-year survival probabilities (95% CI) were 57.7% (56.9–58.6) and 24.1% (23.3–24.8), respectively. Stratification by diagnosis year showed consistent improvements in survival over time ( p < 0.0001 for trend). Median OS was 12, 14, 15, 18, and 19 months in successive cohorts. Conclusions: OS in patients diagnosed with unresectable, stage III NSCLC between 2003 and 2013 was consistent with that from clinical studies of sequential/concurrent chemoradiotherapy. Despite improvement over time, median OS was <2 years and mortality remained high during the first year post-diagnosis.

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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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Trends in immunotherapy use and survival impact in stage IV non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20715 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e20715-e20715

Author(s):

Zachary Otaibi ◽

Amir Kamran ◽

Rodney E Wegner ◽

Athanasios Colonias ◽

Benny Weksler ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Private Insurance ◽

Stage Iv ◽

Small Cell ◽

Small Cell Lung ◽

Comorbidity Score ◽

Nsclc Patients

e20715 Background: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. 5-year survival rate for metastatic non-small cell lung cancer (NSCLC) is estimated at 4%. For patients who lack a driver mutation, platinum based chemotherapy had been the cornerstone treatment, but the addition of immunotherapy has altered the treatment landscape for many advanced NSCLC patients. Immunotherapy, with or without chemotherapy, has been demonstrated in many clinical trials to extend survival in both the first-line setting as well as subsequent lines of therapy. While the clinical trial data over the past several years has been robust, less is known about how these agents have fared in routine clinical practice. To understand this better, we utilized the National Cancer Data Base (NCDB) to examine the survival of patients who received immunotherapy for stage IV NSCLC. Methods: We queried the NCDB from 2004-2015 for patients with stage IV NSCLC treated with chemotherapy and at least 3 months of follow-up. Multivariable logistic regression was used to determine predictors of immunotherapy use. Multivariable cox regression was used to determine predictors of overall survival. A propensity score was calculated and used to mitigate indication bias. Results: Of 203,069 eligible patients, 5,877 received immunotherapy. The median age was 65 years (40-90). The median follow up was 10.6 months (3-154). Patients were more likely to receive immunotherapy if they were younger, had a lower comorbidity score, received treatment at an academic facility, had adenocarcinoma histology, private insurance, Caucasian race, and a more recent treatment year. The use of immunotherapy rose steadily across the dataset years, rising from 1% to 12%. Predictors of survival were younger age, lower comorbidity score, lower grade tumor, treatment at an academic facility, higher education, higher income, private insurance, metropolitan location, immunotherapy use, adenocarcinoma histology, and more recent year of treatment. On propensity-matched Kaplan-Meier analysis patients treated with immunotherapy in addition to chemotherapy had improved survival, 13.7 months compared to 11.8 months, p < 0.0001. Conclusions: This analysis demonstrates improved overall survival in stage IV NSCLC patients who received immunotherapy. There are inherent limitations of retrospective analyses of data from large databases, however the survival improvement noted in this study is concordant with the more robust prospective clinical research published to date.

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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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279 Durvalumab after chemoradiotherapy for PD-L1 expressing inoperable stage III NSCLC impacts local-regional control and overall survival

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0279 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A304-A304

Author(s):

Lukas Kaesmann ◽

Julian Taugner ◽

Chukwuka Eze ◽

Claus Belka ◽

Farkhad Manapov

Keyword(s):

Overall Survival ◽

Real World ◽

Stage Iii ◽

Historical Cohort ◽

Free Survival ◽

Regional Control ◽

Stage Iii Nsclc ◽

Local Regional Control ◽

Nsclc Patients

BackgroundChemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study aims to evaluate the oncological outcome of patients treated with CRT alone to those treated with CRT and durvalumab (CRT-IO) in the real-world setting.MethodsRetro- and prospectively collected data of 133 consecutive inoperable stage III NSCLC patients treated between 2011–2019 were evaluated. Local-regional-recurrence-free-survival (LRPFS - defined as progression in the mediastinum, hilum and/or supraclavicular region at both sides and the involved lung), progression-free survival (PFS) and overall survival (OS) were evaluated from last day of thoracic radiotherapy (TRT).ResultsMedian age at diagnosis was 68.5 years; 44 (33%) were female; 58 (44%) were diagnosed with adenocarcinoma. All patients were irradiated to a total dose of at least 60 Gy (EQD2). Median PTV was 709.8 cc (range: 181–1958 cc). 113 (85%) patients were treated with CRT and 20 (15%) PD-L1 expressing patients with CRT-IO. 83% of patients received two cycles of concomitant platinum-based chemotherapy. Median time to initiation of durvalumab after CRT was 0.8 months (range: 0.4–2.1). Median follow-up for entire cohort was 33.3 months (range: 4.8–111.8) and median overall survival (OS) was 24.7 (95% CI: 18.9–30.4) months. In the CRT-IO cohort after a median follow-up of 15.5 (range: 5.1–20.2) months, no deaths were reported at the time of evaluation (August 2020). Improved LRPFS (p=0.013), PFS (p=0.033) and OS (p=0.002) were correlated with CRT-IO compared to the historical cohort of conventional CRT patients.After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume and treatment mode and exact matching for T-and N-stage, 18 CRT-IO patients were matched 1:2 to 36 CRT patients. 12-month LRPFS, PFS and OS rates in the CRT-IO vs CRT cohort were 80% vs 38.8% (p=0.001), 50% vs 22% (p=0.013) and 100% vs 75% (p=0.002), respectively. Also regarding intracranial failure, 6-month brain metastases rates were 0% vs. 6% in the CRT-IO vs CRT cohort (p=0.290).ConclusionsThis real-world analysis demonstrates that durvalumab after CRT has led to significant improvement of local-regional control, PFS and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.AcknowledgementsThe study was partly presented at 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO).Trial RegistrationN/AEthics ApprovalThe study was approved by Ludwig-Maximilians-University (LMU), Munich, Germany: Institution’s Ethics Board, approval number 17-230.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

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Durvalumab after Chemoradiotherapy for PD-L1 Expressing Inoperable Stage III NSCLC Leads to Significant Improvement of Local-Regional Control and Overall Survival in the Real-World Setting

Cancers ◽

10.3390/cancers13071613 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1613

Author(s):

Julian Taugner ◽

Lukas Käsmann ◽

Chukwuka Eze ◽

Amanda Tufman ◽

Niels Reinmuth ◽

...

Keyword(s):

Overall Survival ◽

Real World ◽

Progression Free Survival ◽

Stage Iii ◽

Historical Cohort ◽

Free Survival ◽

Stage Iii Nsclc ◽

Local Regional Control ◽

Nsclc Patients

Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.

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KRAS G12C mutation associated outcomes among patients with locally advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21079 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21079-e21079

Author(s):

David Qian ◽

Madhusmita Behera ◽

Conor Ernst Steuer ◽

Suchita Pakkala ◽

Jennifer W Carlisle ◽

...

Keyword(s):

Somatic Mutation ◽

Locally Advanced ◽

Small Cell ◽

The Cancer Genome Atlas ◽

Stage Iii ◽

Precision Oncology ◽

Small Cell Lung ◽

Kras Mutations ◽

Stage Iii Nsclc ◽

Nsclc Patients

e21079 Background: Recent progress in targeted therapy includes the demonstration of promising anti-tumor activity and safety of a KRAS inhibitor in patients with advanced malignancies harboring the G12C somatic mutation ( KRASG12C). KRAS mutations are present in one-third of all non-small cell lung cancers (NSCLCs), of which KRASG12C comprises about 40%. In this study we characterize the outcomes of patients with stage III NSCLC who received radiotherapy, stratified by KRASG12C status. Methods: Level 3 data for NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA). Clinical and somatic mutation data were analyzed for the 118 NSCLC patients with stage III disease whose treatment included radiotherapy with or without chemotherapy. Overall survival (OS) and progression-free survival (PFS) were then compared between patients whose tumors possess versus lack KRASG12C using Cox proportional hazards regression. Results: This TCGA cohort study consists of 75 males and 43 females with stage III NSCLC (57 adenocarcinomas and 61 squamous cell carcinomas) enrolled between February 2010 and November 2014. Presence of KRASG12C was detected in 7 patients (6%) and conferred poorer OS (HR 3.14, 95% CI 1.12–8.84, P = 0.030) as well as PFS (HR 3.74, 95% CI 1.46–9.56, P = 0.0059) compared to absence of KRASG12C, with median survival of 9.0 versus 28.9 months and median time to progression of 8.5 versus 16.8 months. All 7 patients with KRASG12C had lung adenocarcinomas (ACs). Inferior survival of patients with KRASG12C persisted on subgroup analyses of AC and KRAS mutation status (Table). Conclusions: Among patients with stage III NSCLC in TCGA treated by radiotherapy, those with KRASG12C had significantly worse OS and PFS. Clinical trial of a KRAS inhibitor is a rational next step toward improving outcomes for this patient population, which has yet to be remarkably impacted by existing precision oncology approaches. [Table: see text]

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Concurrent Palliative Chemoradiotherapy versus Definitive Chemoradiotherapy in Poor Prognosis Stage III non-small-cell lung cancer

QJM ◽

10.1093/qjmed/hcaa057.006 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

M A Elkhafif ◽

M Elbassiouny ◽

K Elhusseny ◽

D Salem ◽

A Shafik

Keyword(s):

Lung Cancer ◽

Low Dose ◽

Locally Advanced ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Definitive Chemoradiation ◽

Stage Iii Nsclc ◽

Carboplatin Auc

Abstract Background The palliative role of chemoradiation in treatment of patients with locally advanced non-small-cell lung cancer remains unresolved; Controversy remains about whether long term and high doses radiotherapy provide better results than short course schedules in treatment of inoperable stage III NSCLC and negative prognostic factors poor performance status (PS), large tumor, poor pulmonary functions and comorbidities.Hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time. Methods One hundred and ten patients with locally advanced stage III NSCLC with poor prognosyic factors were randomized to receive either definitive chemoradiation or palliative chemoradiation in cancer department of faculty of medicine of AIN SHAMS UNIVERSITY .Arm (A) patients will receive induction chemotherapy with two cycles of carboplatin(AUC6) and paclitaxel 175mg/m²) cycles every 21 day, the third cycle administrated with radiotherapy with low dose of carboplatin(AUC 2) and paclitaxel 60 mg/m² on day 1& 8 administrated concomitant with the radiotherapy 42 Gy over 15 fraction over 3 weeks. Arm (B) patients will receive standard-dose fractionation of radiation 60Gy/6 weeks 2Gy once per day with concurrent weekly low dose of carboplatin (AUC 2) and paclitaxel 60 mg/m² followed by two cycles of full doses of carboplatin (AUC 6) /paclitaxel 175mg/ m² every 21 days.the primary end points were overall survival and progression free survival;secondary end points were health related quality of life(HRQOL) and toxicity. Results The median follow-up duration was 24 months in surviving patients’ .Median survival and 2-year OS were in concurrent palliative chemoradiation arm 4.7 and 12.3-months respectively and was 7.3 and 17.6 in concurrent definitive chemoradiatiobn arm respectively (p < 0.01). HRQOL was better in the palliative arm during the treatment but remained unchanged in both arms during the follow up visits. There were more hospital admissions related to side effects in the definitive chemoradiation arm (p < 0.05). Conclusions This study confirmed that the definitive chemoradiation was superior to palliative chemoradiation arm with respect to survival.the treatment related toxicity and HRQOL were better in the palliative chemoradiation arm than the definitive arm.

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