Stage IIIB NSCLC Research Articles

EP.08D.07 Pathological Response to Neoadjuvant Tislelizumab Plus Chemotherapy in Potentially Resectable Stage IIIB NSCLC

EP.08D.07 Pathological Response to Neoadjuvant Tislelizumab Plus Chemotherapy in Potentially Resectable Stage IIIB NSCLC

Circulating Growth Differentiation Factor 15 as a Biomarker in Patients with Unresected Locally Advanced Non-Small Cell Lung Cancer Treated with Chemo-Radiotherapy with or without Metformin

Growth differentiation factor 15 (GDF15) is a member of the TGFβ family suggested to have prognostic value in cancer. Plasma GDF15 levels are elevated in humans during cellular stress, chronic diseases, and cancer and in response to cytotoxic (chemotherapy and radiation) or metabolic (metformin) therapies. Currently, the effect of combined metformin and cytotoxic treatment on circulating GDF15 is not known, and it is unclear whether GDF15 can serve as a biomarker in patients receiving such therapy. To examine this question, we analyzed circulating GDF15 levels in stage IIIA or IIIB NSCLC patients that participated in the randomized phase II clinical trial OCOG-ALMERA (NCT02115464). In OCOG-ALMERA patients were randomized to treatment with concurrent platinum-based chemotherapy and chest radiotherapy (60-66 Gy), with or without consolidation chemotherapy (CRT) or the same treatment plus metformin (2000mg/d). Dosimetric parameters and survival outcomes were collected by the trial. EDTA Plasma was collected from patients at baseline, 2 weeks into CRT treatment, at completion of CRT and 6 months after treatment initiation and assayed for GDF15 using an ELISA method. Statistical analyses were conducted to explore potential associations between plasma GDF15 with survival and dosimetric parameters. Fifteen patients from the metformin arm and 18 from the control arms provided EDTA plasma for this analysis. Average baseline GDF15 levels for all participants were elevated compared to those reported for healthy individuals. Baseline plasma GDF15 was statistically prognostic for RFS and OS (hazard ratio = 1.19, 95% CI = 1.06 to 1.34, p = 0.005). GDF15 levels increased during CRT treatment reaching the highest value at the end of cytotoxic therapy. Addition of metformin to CRT treatment was associated with further increase in circulating GDF15 (p<0.001). Plasma GDF15 levels at 2 weeks of CRT were positively correlated with size of the radiotherapy clinical target volume and volumes of esophagus and heart receiving high dose radiotherapy. This work suggests that GDF15 may be a promising prognostic marker to predict response to standard chemoradiation therapy in NSCLC. Future studies should aim to validate these results in larger datasets and examine whether GDF15 may have value as early biomarker of radiation toxicity in lung cancer patients.

Efficacy and surgical safety of sequential surgical resection after pembrolizumab plus chemotherapy for initial unresectable stage IIIB non-small cell lung cancer

IntroductionNeoadjuvant immunochemotherapy is effective in resectable NSCLC. However, its role in unresectable stage IIIB NSCLC patients remains controversial. This study aimed to demonstrate the efficacy and safety of neoadjuvant immunochemotherapy followed by surgical resection to treat initial unresectable stage IIIB NSCLC patients. MethodsThis study retrospectively analyzed 59 initial unresectable stage IIIB NSCLC patients who received induction pembrolizumab combined with chemotherapy between June 2019 and April 2022. Clinical characteristics, radiological and pathological responses, and survival outcomes were collected and evaluated. ResultsFifity-nine initial unresectable stage IIIB NSCLC patients were identified and divided into surgery (n = 23) and non-surgery (n = 36) groups with a median follow-up time of 15.0 months. The median PFS/DFS of the surgery group was significantly longer than the non-surgery group (not reached vs. 15.5 months, p = 0.0031). The median overall survival (OS) was not reached in both groups, and the OS rate was 100% (23/23) in the surgery group and 83.3% (30/36) in the non-surgery group. The pathological analysis suggested that 13 of 23 patients (56.5%) achieved major pathological response (MPR) or pathological complete response (pCR), and more squamous cell carcinoma cases were observed in the MPR group compared to the non-MPR group (p = 0.034). All patients in the surgery group had an R0 resection, and no surgical-related mortality was recorded; only three patients (13.0%) experienced any postoperative complications. ConclusionIn this retrospective study, surgical resection after neoadjuvant immunochemotherapy was promising for initial unresectable stage IIIB NSCLC patients, with a high MPR rate and good surgical safety.

Nomogram predicting overall survival of stage IIIB non-small-cell lung cancer patients based on the SEER database.

We aimed to evaluate the prognostic value of stage IIIB non-small-cell (NSCLC) lung cancer patients and to construct a nomogram to effectively predict their overall survival (OS). In total, 4323 patients with stage IIIB NSCLC diagnosed between 1975 and 2018 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple prognostic factors were combined to construct a nomogram for predicting OS of patients with stage IIIB NSCLC. The discrimination and calibration of the nomogram were evaluated by C-indexes and calibration curves. The nomogram was evaluated for predictive ability using receiver operating characteristic (ROC) curves, decision curve analysis curve (DCA), and clinical impact curve (CIC). The nomogram was built on data of 4323 patients with stage IIIB NSCLC and consisted of the following prognostic factors: age, race, sex, primary labeled, pathology, T stage, whether to receive surgery, whether to receive radiotherapy, and whether to receive chemotherapy. The C-index in the training and validation sets for the nomogram was 0.672 (95% CI: 0.661-0.683) and 0.675 (95% CI: 0.656-0.694), respectively. According to scores of the nomogram, patients in the complete set, validation set, and training set were classified into two risk groups, low risk and high risk. We developed the first validated nomogram to estimate the OS of patients with stage IIIB NSCLC. The nomogram was based on nine prognostic factors and provided an individualized risk estimate of 3-year and 5-year OS survival in patients with stage IIIB NSCLC.

Aumolertinib with chemotherapy or alone compared with osimertinib in patients with EGFR-mutant non–small-cell lung cancer (TREBLE).

TPS9153 Background: Aumolertinib is a novel third-generation (3G) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Safety and efficacy of aumolertinib have been demonstrated in patients with EGFR-mutated locally advanced or metastatic (LA/m) NSCLC. (Lu, 2021; Lu, 2022) A phase 3 study in these patients in the first-line setting showed a significant improvement in progression-free survival (PFS) for aumolertinib vs gefitinib (median 19.3 months versus 9.9 months; P &lt; 0.0001). Aumolertinib was generally well-tolerated. (Lu, 2022) Aumolertinib is approved in China for patients with LA/m NSCLC who have an EGFR T790M resistance mutation upon disease progression and for treatment naïve patients with EGFR-mutated NSCLC. Studies evaluating first-generation EGFR-TKI + chemotherapy (chemo) showed improved PFS in select patient populations. (Hosomi, 2019) It is unclear if the addition of chemo to a 3G EGFR-TKI will improve PFS in patients with EGFR-mutated LA/m NSCLC. As the addition of chemo to a 3G EGFR-TKI may prove warranted, there is a need to understand the relative efficacy and safety in the diversity of patients encountered in routine clinical practice. (Tanaka, 2021). Methods: This is a randomized, multi-regional, phase 3 clinical trial comparing aumolertinib + chemo or aumolertinib monotherapy with osimertinib monotherapy. Patients are eligible if they have stage IIIB, IVA, or IVB NSCLC; harbor ex19del or L858R EGFR mutations alone or with other EGFR mutations; and have an ECOG PS of ≤2. Patients are ineligible if they received prior systemic therapy for mNSCLC or are a candidate for curative intent therapy. Eligible patients will be randomized 2:2:1 and stratified by mutation status (ex19del or L858R), ECOG PS (0 vs 1/2), and race (White vs Asian vs other races combined). Anticipated enrollment is 500 patients; 200 to receive aumolertinib + chemo (110 mg PO QD aumolertinib + investigator's choice chemo), 200 to receive osimertinib (80 mg PO QD), and 100 to receive aumolertinib (110 mg PO QD). The primary endpoint is PFS, by blinded independent review committee (BICR) per RECIST 1.1, for aumolertinib + chemo vs osimertinib. Overall survival (OS) is a key secondary endpoint for aumolertinib + chemo vs osimertinib. Additional efficacy endpoints will be assessed for aumolertinib + chemo vs osimertinib and aumolertinib vs osimertinib, as well as safety and patient reported outcomes. Exploratory endpoints include characterizing mechanisms of acquired resistance across all arms, CNS efficacy, and exposure-response relationship. Enrollment began in July 2022. The study is currently recruiting and will include approximately 200 sites globally. The study design will provide a power of 80% at a 2-sided Type I error of 0.05 for the primary endpoint. If the primary endpoint is statistically significant, a sequential test method will be used to evaluate OS. Clinical trial information: NCT05493501 .

Efficacy and safety of pembrolizumab plus chemotherapy and sequential surgical resection in initial unresectable stage IIIB NSCLC.

e20595 Background: Neoadjuvant immunochemotherapy has been proved effective in resectable NSCLC, while its role in unresectable stage IIIB NSCLC remains controversial. This study aims to demonstrate the efficacy and safety of neoadjuvant immunochemotherapy sequential surgical resection in initial unresectable stage IIIB NSCLC patients. Methods: This multicenter study retrospectively analyzed 59 patients with initial unresectable stage IIIB NSCLC who received induction pembrolizumab combined with chemotherapy between June 2019 and April 2022. The clinical characteristics, radiological and pathological response and survival outcomes were collected and evaluated. Results: A total of 59 initial unresectable stage IIIB NSCLC patients were identified and divided into the surgery group (n = 23) and non-surgery group (n = 36) with a median follow-up time of 15.0 months. The median PFS/DFS of surgery group was significantly longer than that of non-surgery group (not reached versus 15.5 months, p = 0.0031). The median OS was not reached in both groups, overall survival rate was 100% (23/23) in surgery group and 83.3% (30/36) in non-surgery group. Pathological analysis suggested that 13 of 23 patients (56.5%) achieved major pathological response (MPR) or pathological complete response (pCR), and more squamous cell carcinoma cases were observed in MPR group compared to non-MPR group ( p = 0.034). Of 23 patients in surgery group, all patients had a R0 resection, no surgical-related mortality was recorded, only 3 patients (13.0%) experienced any postoperative complications. Conclusions: Surgical resection after neoadjuvant immunochemotherapy is beneficial in the survival outcome of initial unresectable stage IIIB NSCLC patients, with a high MPR rate and good surgical safety.

56O A randomized, controlled, multicenter phase II trial of camrelizumab combined with albumin-bound paclitaxel and cisplatin as neoadjuvant treatment in resectable stage IIIA and IIIB (T3N2) non-small-cell lung cancer

Resectable NSCLC with neoadjuvant chemotherapy(CT) has favourable outcomes. However, with few neoadjuvant immunotherapy trials, detailed information on patients(pts) with resectable stage IIIA and IIIB(T3N2) NSCLC is available. Camrelizumab(Cam), a PD-1 antibody, has shown a survival benefit in patients with advanced NSCLC. However, the antitumor activity and safety of Cam plus CT in the neoadjuvant setting is unknown. Here, we report the final analysis from this multi-center, open-label, randomized controlled phase II trial.

Tumor angiogenesis at baseline identified by 18F-Alfatide II PET/CT may predict survival among patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

BackgroundThe study investigated the predictive value of tumor angiogenesis observed by 18F-ALF-NOTA-PRGD2 II (denoted as 18F-Alfatide II) positron emission tomography (PET)/computed tomography (CT) before concurrent chemoradiotherapy (CCRT) for treatment response and survival among patients with locally advanced non-small cell lung cancer (LA-NSCLC).MethodsPatients with unresectable stage IIIA or IIIB NSCLC (AJCC Cancer Staging 7th Edition) who received CCRT were included in this prospective study. All patients had undergone 18F-Alfatide PET/CT scanning before CCRT, and analyzed parameters included maximum uptake values (SUVmax) of primary tumor (SUVP) and metastatic lymph nodes (SUVLN) and mean uptake value of blood pool (SUVblood). Tumor-to-background ratios (TBRs) and changes in tumor diameter before and after CCRT (ΔD) were calculated. The ratios of SUVP to SUVblood, SUVLN to SUVblood, and SUVP to SUVLN were denoted as TBRP, TBRLN, and T/LN. Short-term treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.ResultsOf 38 enrolled patients, 28 completed CCRT. SUVP, SUVLN, TBRP, TBRLN and T/LN showed significant correlation with PFS (all P < 0.05). SUVP was negatively correlated with OS (P = 0.005). SUVP and TBRP were higher in non-responders than in responders (6.55 ± 2.74 vs. 4.61 ± 1.94, P = 0.039; 10.49 ± 7.58 vs. 7.73 ± 6.09, P = 0.023). ΔD was significantly greater in responders (2.78 ± 1.37) than in non-responders (-0.16 ± 1.33, P < 0.001). Exploratory receiver operating characteristic curve analysis identified TBRP (area under the curve [AUC] = 0.764, P = 0.018), with a cutoff value of 6.52, as the only parameter significantly predictive of the response to CCRT, with sensitivity, specificity, and accuracy values of 71.43%, 78.57%, and 75.00%, respectively. ROC curve analysis also identified SUVP (AUC = 0.942, P < 0.001, cutoff value 4.64) and TBRP (AUC = 0.895, P = 0.001, cutoff value 4.95) as predictive of OS with high sensitivity (84.21%, 93.75%), specificity (100.00%, 66.67%), and accuracy (89.29%, 82.14%).ConclusionsEvaluation of tumor angiogenesis by 18F-Alfatide II at baseline may be useful in predicting the short-term response to CCRT as well as PFS and OS in patients with LA-NSCLC.

Radical Minimally Invasive Surgery After Immuno-chemotherapy in Initially-unresectable Stage IIIB Non-small cell Lung Cancer.

Use of neoadjuvant immunotherapy agent in advanced stage NSCLC is controversial. Herein, we aim to report on a case series of successful conversion from initial unresectable stage cIIIB NSCLC to radical minimally invasive surgery through immunochemotherapy; with particular attention given to surgical outcomes and survival benefit of surgery. Fifty-one patients with initial stage cIIIB NSCLC who received PD-1 agents plus platinum-based chemotherapy between May, 2018 to August, 2020 were retrospectively identified. Surgical and oncological outcomes of enrolled patients were collected. Of 31 patients who underwent subsequent resection, 23 (74.2%) patients underwent lobectomy, 1 (3.2%) underwent pneumonectomy, 5 (16.1%) underwent sleeve lobectomy, and 2 (6.5%) with bilobectomy. The median surgical time was 205 minutes (range, 100-520). The average blood loss was 185 (range: 10-1100) ml. Dense adhesions or fibrosis was noted in 15 cases. The median postoperative hospital stay was 6 (range: 3-13) days. No surgical-related mortality was recorded, only 5 patients (16.1%) experienced any postoperative morbidity (no grade 3 complications). Ten patients (32.3%) had major pathological response, with mediastinal down-staging been observed in 22/31 (71.0%) patients. With a median after up of 15.4 months, thirty-one patients that had surgery had relatively longer median DFS/PFS compared to that of either non-responders or responders that without surgery (27.5 vs. 4.7 vs. 16.7 months, respectively). Radical surgery after chemoimmunotherapy in initial unresectable stage IIIB NSCLC seems to be safe with low surgical-related mortality and morbidity, and was favorably associated with longer DFS/PFS compared to those without surgery.

Abstract PO-059: Investigating gene expression profiles associated with clinical radiation resistance in KEAP1/NFE2L2 wildtype lung cancer

Abstract Background: We previously reported that approximately half of local recurrences (LR) after radiotherapy for localized NSCLC harbor mutations in KEAP1 or NFE2L2. Here we sought to explore factors associated with LR after radiotherapy in KEAP1/NFE2L2 wildtype NSCLC. Methods: We identified consecutive patients with stage IA1-IIIC NSCLC treated at our institution with chemoradiotherapy (CRT) or stereotactic ablative radiotherapy (SABR) from 2009-2018 and who had genotyping performed on tumor tissue with full coverage of common recurrent lung cancer driver genes including TP53, KRAS, KEAP1, and NFE2L2. We defined LR as tumor regrowth within the prescription dose radiotherapy volume. Our primary objective was to identify factors associated with LR in KEAP1/NFE2L2WT tumors. We performed RNA-seq on a subset of cases with available tissue using the SMARTer Stranded total RNA-seq Kit v2 (Takara Bio USA, Inc.). Statistical analysis was performed using R (version 3.6) with differential gene expression performed using ‘DESeq2’. All P-values were two-sided and considered significant at P&amp;lt;0.05 with adjustment for multiple hypothesis testing when appropriate. Results: We identified 139 consecutive patients with localized NSCLC who received tumor genotyping and were treated with CRT for stage IIB-IIIC NSCLC (n=58) or SABR for stage I-IIB NSCLC (n=81). 26 (18.7%) of these patients harbored KEAP1/NFE2L2WT tumors. Clinical factors such as tumor volume (P=0.18), histology (P=0.87), and radiation dose (P=0.3) were not associated with LR in this subset. Similarly, somatic mutation analysis did not reveal association of any recurrent driver mutations with LR in these KEAP1/NFE2L2WT tumors, including in TP53 (n=19; P=0.73) or KRAS (n=9; P=0.98). Tissue was available for RNA-seq analysis of 38 KEAP1/NFE2L2WT tumors, of which the majority were adenocarcinomas (n=25, 65.8%) and approximately half each received CRT (n=20, 52.6%) and SABR (n=18, 47.4%). Gene set enrichment analysis revealed a trend for association of LR with expression of hypoxia genes (P=0.07, Q=0.28). Similarly, a previously reported 10-gene radiation sensitivity index (RSI) was not associated with LR (P=0.34). Individual gene analysis identified KRT14 as being significantly less expressed in cases with LR (adjusted P=2.2e-9). In a validation cohort of 24 stage I-IIA KEAP1/NFE2L2WT patients from the TCGA who were treated with radiotherapy, those who died had lower expression of KRT14 than those who did not (P=0.0003). Conclusions: In summary, we identify low expression of KRT14, a squamous cell carcinoma differentiation gene, as a potential biomarker for increased risk of LR after definitive radiotherapy of KEAP1/NFE2L2WT NSCLC. Validation in larger cohorts and biological characterization will be required to determine if this biomarker could be useful for guiding precision radiotherapy approaches. Citation Format: Michael S. Binkley, Young-Jun Jeon, Monica Nesselbush, Everett J. Moding, Barzin Nabet, Diego Almanza, Christopher Yoo, David M. Kurtz, Susie Grant Owen, Leah M. Backhus, Mark F. Berry, Joseph B. Shrager, Kavitha J. Ramchandran, Sukhmani K. Padda, Millie Das, Joel W. Neal, Heather A. Wakelee, Ash A. Alizadeh, Billy W. Loo, Maximilian Diehn. Investigating gene expression profiles associated with clinical radiation resistance in KEAP1/NFE2L2 wildtype lung cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-059.

P02.10 Patterns of Care for Elderly Patients over Age 80 with Stage IIIA-N2, IIIB, and IIIC NSCLC

P02.10 Patterns of Care for Elderly Patients over Age 80 with Stage IIIA-N2, IIIB, and IIIC NSCLC

Pretreatment systemic inflammation response index (SIRI) is an independent predictor of survival in unresectable stage III non-small cell lung cancer treated with chemoradiotherapy: a two-center retrospective study.

BackgroundCirculating immune cells influence the efficacy of cancer therapy. This study aimed to investigate the prognostic values of different peripheral blood leukocyte (PBL) biomarkers in non-small lung cancer (NSCLC) patients treated with chemoradiotherapy.MethodsAn independent cohort of 176 stage III NSCLC patients who were diagnosed at Shanghai Pulmonary Hospital and Zhejiang Cancer Hospital between April, 2010, and September, 2018, and had available pretreatment peripheral blood tests was enrolled. The patients were all treated with concurrent or sequential chemoradiotherapy according to international clinical guidelines, with conventional fractionated radical radiotherapy. The receiver operating characteristic curve and the Youden index were used to determine the optional cutoff values of PBL biomarkers for distinguishing prognosis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the factors significantly correlated with overall survival.ResultsThe cohort had a median follow-up time of 21.7 (3.1–121) months. The 3- and 5-year OS rates of all patients were 34.7% and 27.5%, respectively. Univariate analysis showed that gender (P=0.011), smoking (P=0.011), tumor-node-metastasis (TNM) stage (P=0.002), pretreatment peripheral blood neutrophil-to-leukocyte ratio (P=0.013), and systemic inflammation response index (SIRI, P<0.001) were all correlated with OS in NSCLC patients. Moreover, multivariate analysis revealed that TNM stage (HR =1.541, 95% CI: 1.166–2.036, P=0.010) and SIRI (HR =1.868, 95% CI: 1.016–3.436, P=0.018) were significantly and independently associated with OS. However, the median OS of stage IIIB NSCLC patients with low SIRI (≤2.0) was longer than that of stage IIIA NSCLC patients with high SIRI (>2.0) (33.9±4.1 vs. 19.6±2.5 months).ConclusionsPretreatment peripheral blood SIRI was found to be a simple independent predictor of OS in stage III NSCLC patients who underwent chemoradiotherapy. As a novel prognostic marker, the prognostic value of the SIRI is superior to that of the NLR. Low SIRI could be a better prognostic stratification factor for NSCLC patients with different TNM stages.

STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort

IntroductionSomatic mutations in STK11 and KEAP1, frequently comutated in non-squamous non-small cell lung cancer (NSQ NSCLC), have been associated with poor response to immune checkpoint blockade (ICB). However, previous reports lack non-ICB controls needed to properly ascertain the predictive nature of those biomarkers. The objective of this study was to evaluate the predictive versus prognostic effect of STK11 or KEAP1 mutations in NSQ NSCLC.MethodsPatients diagnosed with stage IIIB, IIIC, IVA or IVB NSQ NSCLC from a real-world data cohort from the Flatiron Health Network linked with genetic testing from Foundation Medicine were retrospectively assessed. Real-world, progression-free survival (rwPFS) and overall survival (OS) were calculated from time of initiation of first-line treatment.ResultsWe analysed clinical and mutational data for 2276 patients including patients treated with anti-programmed death-1 (PD-1)/anti-programmed death ligand 1 (PD-L1) inhibitors at first line (n=574). Mutations in STK11 or KEAP1 were associated with poor outcomes across multiple therapeutic classes and were not specifically associated with poor outcomes in ICB cohorts. There was no observable interaction between STK11 mutations and anti-PD-1/anti-PD-L1 treatment on rwPFS (HR, 1.05; 95% CI 0.76 to 1.44; p=0.785) or OS (HR, 1.13; 95% CI 0.76 to 1.67; p=0.540). Similarly, there was no observable interaction between KEAP1 mutations and treatment on rwPFS (HR, 0.93; 95% CI 0.67 to 1.28; p=0.653) or OS (HR, 0.98; 95% CI 0.66 to 1.45; p=0.913).ConclusionOur results show that STK11-KEAP1 mutations are prognostic, not predictive, biomarkers for anti-PD-1/anti-PD-L1 therapy.

1558P - Biomarker status as a mediator of age-related overall survival (OS) in advanced non-small cell lung cancer (aNSCLC)

BackgroundRisk models for NSCLC have identified age as a prognostic factor, but the relevance of molecular biomarkers to age-related outcomes is undefined. We explored the prevalence of biomarkers by age group and the impact of biomarker status on age-related differences in OS among aNSCLC patients (pts) in a real-world population. MethodsPts with stage IIIB, IV or recurrent metastatic NSCLC (diagnosed 1/1/11 to 11/30/18) were identified in a US-based, EHR-derived, deidentified database (Flatiron Health). Cox proportional hazard regressions evaluated OS by age at aNSCLC diagnosis (dx) (< vs≥50 years), controlling for gender, histology, race, stage, dx year, smoking status, visit site, region and PDL1 status. Sequential and subgroup regressions modeled ALK+, EGFR+ and ROS1+ biomarker status as mediators of the age effect on OS. ResultsOur sample included 41,024 pts (median age 69 years); median OS was 11 months. Pts <50 years lived longer than pts ≥50 years (HR: 0.83; p<0.001). Molecular testing and positive results for ALK, EGFR and ROS1 were higher in age <50 (Table); this finding was maintained for non-squamous pts (p≤0.001). Within ALK+, EGFR+ or ROS1+ subgroups, age was not associated with OS. Sequential variable analysis found 35% of the association between age and OS may be explained by ALK, EGFR and ROS1 biomarker status. ConclusionsYoung aNSCLC pts have longer OS than older pts; this benefit is significantly mediated through biomarker status. Pts with mutations had similar OS regardless of age group. As older pts are tested less often and have a lower prevalence of mutations, future work should explore whether increased testing in older pts may mitigate the age-related OS disparity.Table1558P Baseline characteristics by age at aNSCLC Dx*TableAll, n (%) N=41,024< 50 y, n (%) n=1381≥50 y, n (%) n=39,643Female19,301 (47)716 (52)18,585 (47)Non-squamous histology28,203 (69)1092 (79)27,111 (68)Non-smoker4723 (12)323 (23)4400 (11)ALK tested23,618 (58)948 (69)22,670 (57)ALK+†625 (2.6)106 (11)519 (2.3)EGFR tested25,276 (62)1000 (72)24,276 (61)EGFR+†3009 (12)162 (16)2847 (12)ROS1 tested12,310 (30)514 (37)11,796 (30)ROS1+†113 (0.92)12 (2.3)101 (0.86)*All age comparisons p<0.001;†among tested Legal entity responsible for the studyFlatiron Health. FundingFlatiron Health. DisclosureA.B. Cohen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, an independent subsidiary of Roche; Shareholder / Stockholder / Stock options: Roche. B.D.A.P. Neri: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, an independent subsidiary of the Roche group. B.J.S. Adamson: Full / Part-time employment, Provisional patent filed: Flatiron Health, an independent subsidiary of Roche; Non-remunerated activity/ies, Provisional patent filed: University of Washington; Research grant / Funding (self): American Foundation for Pharmaceutical Education; Research grant / Funding (institution): PhRMA Foundation; Leadership role: International Society for Pharmacoeconomics and Outcomes Research; Advisory / Consultancy: Salutis Consulting; Advisory / Consultancy: Fred Hutchinson Cancer Research Center; Advisory / Consultancy: Institute for Disease Modeling, Intellectual Ventures; Advisory / Consultancy: Boston Scientific; Shareholder / Stockholder / Stock options: Roche. C.M. Scanlon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, an independent subsidiary of Roche. C. Gross: Honoraria (self), Travel / Accommodation / Expenses: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Johnson & Johnson. N.J. Meropol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Roche. R.A. Miksad: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Roche; Advisory / Consultancy: De Luca Foundation.

Abstract LB-016: Radiochemotherapy combined with NK cells followed by a second-line PD-1 inhibition in a patients with NSCLC stage IIIb induces long-term tumor control

Abstract Advanced stage NSCLC is a fatal disease with poor prognosis. Following radiochemotherapy (RCT) tumor progression occurs after 5.6 months in stage III NSCLC patients. We identified membrane heat shock protein 70 (mHsp70) as a biomarker for high-risk NSCLC. Furthermore, mHsp70 serves as a tumor-specific target for NK cells that had been stimulated with Hsp70-peptide (TKD) and IL-2. In this study, a patient with mHsp70 positive inoperable NSCLC (cT4, cN3, cM0, stage IIIb) was treated for the first time with a combined therapy consisting of RCT (64.8 Gy), 4 cycles of mHsp70-targeting, autologous NK cells and PD-1 antibody, as a second-line therapy. Adoptive transfer of ex vivo Hsp70-activated NK cells after RCT combined with PD-1 inhibition was well tolerated and resulted in a superior OS. No viable tumor cells, but a massive immune cell infiltration of T and NK cells in fibrotic tissue were detected after therapy. Neither tumor progression nor distant metastases were detectable by CT-scanning 35 months after diagnosis. Therapy response was associated with significantly increased CD3-/NKG2D+/CD94+ NK cell counts, elevated CD8+ to CD4+ T cell, CD3-/CD56bright to CD3-/CD56dim NK cell ratios, and significantly reduced regulatory T cells (Tregs) in the peripheral blood. In summary, a combined immunotherapy consisting of RCT, mHsp70-targeting NK cells and PD-1 antibody inhibition is well tolerated, induces anti-tumor immune responses and results in long-term tumor control in a patient with advanced NSCLC. Citation Format: Gabriele Multhoff, Konrad Kokowski, Martin Hildebrandt, Peter Vaupel, Stefan Stangl. Radiochemotherapy combined with NK cells followed by a second-line PD-1 inhibition in a patients with NSCLC stage IIIb induces long-term tumor control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-016.

P23 Stage IIIb NSCLC and Curative Intention Treatment: Difficulties and Disparities in Brazil

P23 Stage IIIb NSCLC and Curative Intention Treatment: Difficulties and Disparities in Brazil

Should surgery be part of the multimodality treatment for stage IIIB non-small cell lung cancer?

Traditionally, treatment for stage IIIB (T4N2M0 and T1-4N3M0) NSCLC consists in definitive chemoradiation. Surgery is used only anecdotally. Here, we studied outcome for patients treated with multimodality including surgery. Patients who underwent surgery for stage IIIB between 2000 and 2015 were retrospectively reviewed and data analyzed. Patients were selected for surgery if they would tolerate multimodality treatment, the tumor was deemed upfront resectable, and N2-N3 involvement was limited to a non-bulky single site. Survival was calculated from the date of surgery until last follow-up. Univariate and multivariate analysis were performed to identify prognostic factors. During the study period, 5416 patients underwent resection for NSCLC in our center. Sixty patients (1%) had clinical stage IIIB. Thirty-two patients had T4N2 NSCLC involving the carina and/or superior vena cava (n = 25, 78%), left atrium (n = 5, 16%), or other (n = 2, 6%). Half of the 28 patients with N3-disease had supraclavicular node involvement. Pneumonectomy was performed in 27 patients (45%). Twenty-nine patients (48%) had induction therapy, with chemotherapy alone. Adjuvant therapy was administered to 52 patients (87%), mostly chemoradiation. Complete resection rate was 92%. Post-operative mortality was 3%. Three- and 5-year overall survivals were 51% and 39%, respectively. Multivariate analysis identified incomplete resection (P = 0.008) and absence of adjuvant treatment (P = 0.032) as poor survival prognostic factors. Surgery can be considered as a component of multimodality therapy in highly selected patients with stage IIIB NSCLC based on encouraging 5-year survival of 39%.

1287PD - Preoperative chemotherapy and radiotherapy concomitant to cetuximab in stage IIIB NSCLC: A multicenter phase II SAKK

1287PD - Preoperative chemotherapy and radiotherapy concomitant to cetuximab in stage IIIB NSCLC: A multicenter phase II SAKK

Addition of Surgery After Radiation Significantly Improves Survival in Stage IIIB Non-small Cell Lung Cancer: A Population-Based Analysis.

Limited work, either retrospective or prospective, has been done to investigate whether or not there is a cause-specific mortality (CSM) or all-cause mortality (ACM) benefit to adding surgery following neoadjuvant treatment for Stage IIIB NSCLC. We extracted patients with Stage IIIB NSCLC from the Survival, Epidemiology, and End Results Program (SEER) database treated from 2004 to 2012 with either radiation alone or radiation followed by surgery. Other variables extracted were age, sex, race, and tumor location. The impact of patient and treatment variables on CSM and ACM was explored using Cox multivariable regression analysis. A total of 14,065 patients were extracted from the SEER database. On multivariable analysis, even after adjustment for age, gender, race, and site, radiation followed by surgery was associated with a reduction in cause-specific mortality compared to radiation alone (adjusted HR 0.46; 95% CI 0.41, 0.52; p<0.0001). Median overall survival was 11months in the radiotherapy alone arm versus 29months in the radiotherapy plus surgery arm (p<0.0001 by log-rank test). After adjustment for these same factors, radiation followed by surgery was also associated with a reduction in all-cause mortality compared with radiation alone (adjusted HR 0.47; 95% CI 0.42, 0.52; p<0.0001). Median cause-specific survival was 12months in the radiotherapy alone arm versus 33months in the radiotherapy plus surgery arm (p<0.0001 by log-rank test). In the SEER database, there appears to be both a CSM and ACM benefit to adding surgery following radiation for Stage IIIB NSCLC.

Effect of HLA-DQ presentation on SEG/SEI superantigenic reactivity to a CD4+-mediated anti-tumor response devoid of autoimmune or allogeneic effects.

e21047Background: SEG and SEI are 3rd generation superantigens (SAgs) derived from the enterotoxin gene cluster (egc) of Staphylococcus aureus. In a recent study, 14 patients with stage IIIB NSCLC ...