Abstract Background This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique. Methods This retrospective study included patients with stage III/IV NSCLC treated with a PD-(L)1 inhibitor (nivolumab, pembrolizumab, atezolizumab and durvalumab) at Leiden University Medical Centre and Haga Teaching hospital, (both in The Netherlands) from September 2016 to May 2021. All the relevant data was extracted from the structured and unstructured fields of the Electronic Health Records using a novel text-mining tool. Effectiveness [progression-free survival (PFS) and overall survival (OS)] and safety (the incidence of nine potentially fatal irAEs and systemic corticosteroid requirement) outcomes were compared across age subgroups (young: < 65 years, Middle-aged: 65–74 years, and old: ≥ 75 years) after adjustment for confounding. Results Of 689 patients, 310 patients (45.0%) were < 65 years, 275 patients (39.9%) were aged between 65 and 74 years, and 104 patients (15.1%) were ≥ 75 years. There was no significant difference between younger and older patients regarding PFS (median PFS 12, 8, 13 months respectively; Hazard ratio (HR)middle-aged = 1.14, 95% CI 0.92–1.41; HRold = 1.10, 95% CI 0.78–1.42). This was also the case for OS (median OS 19, 14, 18 months respectively; HRmiddle-aged = 1.22, 95% CI 0.96–1.53; HRold = 1.10, 95% CI 0.79–1.52). Safety analysis demonstrated a higher incidence of pneumonitis among patients aged 65–74. When all the investigated irAEs were pooled, there was no statistically significant difference found between age and the incidence of potentially fatal irAEs. Conclusions The use of PD-(L)1 inhibitors is not associated with age related decrease of PFS and OS, nor with increased incidence of serious irAEs compared to younger patients receiving these treatments. Chronological age must therefore not be used as a predictor for the effectiveness or safety of ICIs.

Introduction: To compare the real-world safety profile of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors between younger and older patients.Materials and Methods: All patients receiving pembrolizumab, nivolumab, atezolizumab or durvalumab between September 2016 and September 2019 at Haga Teaching Hospital, The Hague, The Netherlands were included in this retrospective study. Immune-related adverse drug reactions (irADRs) were manually retrieved from the electronic patient files. The cumulative incidence of irADRs were compared between younger (<65 years) and older (>= 65 years) patients using a Pearsons Chi-square test.Results: We identified 217 patients who were treated with at least one dose of PD-(L)1 inhibitor. 58% were 65 years or older at the start of immunotherapy. 183 patients (84.3%) received monotherapy PD-(L)1 inhibitors and 34 (15.7%) received chemo-immunotherapy. A total of 278 irADRs were registered. Cutaneous irADRs (53.9%), thyroid gland disorders (20.3%), and non-infectious diarrhoea/colitis (17.5%) were the most frequently reported irADRs. The majority of the irADRs were mild to moderate and no fatal irADRs were observed. 61 (21.9%) of the irADRs needed systemic treatment, of which 19 (6.8%) required treatment with corticosteroids. 18 irADRs (6.5%) were severe and resulted in hospitalisation.The cumulative incidence of cutaneous irADRs was different between the age groups: 45.7% of the patients <65 years and in 60.0% of the patients >= 65 years (p = 0.036). No statistical difference was found in the cumulative incidence of other irADRs between the two age groups.Discussion: Advanced age is not associated with immune-related adverse drug reactions of PD-1 and PD-L1 inhibitors.

We analyzed the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) in 142 elderly patients with lung cancer. Potentially frail patients, identified by an impaired G8 or ISAR-HP, had a significantly greater risk of 1-year mortality. Using the ISAR-HP as the only screening tool would be insufficient; however, an impaired ISAR-HP and G8 would lead to fine tuning the selection of patients with multiple geriatric impairments. Background: Because of the time-consuming aspect of geriatric assessments, cancer specialists are seeking shorter screening tools to distinguish fit and frail patients. We analyzed the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) in elderly patients with lung cancer. Patients and Methods: From January 2014 to April 2016, the data from patients with lung cancer aged > 70 years at 2 teaching hospitals in the Netherlands were included in a database. The patients were classified as potentially frail if they had a G8 of <= 14 or ISAR-HP of >= 2. Results: Of the 142 included patients (median age, 77 years; interquartile range, 73-82 years), 108 (76%) were potentially frail. After correction for possible confounders, the potentially frail patients had a significantly greater risk of 1-year mortality (hazard ratio [HR], 4.08; 95% confidence interval [CI] 1.67-9.99; P = .02). Higher disease stage (HR, 1.72; 95% CI, 1.40-2.12; P < .001) was also a significant predictor of mortality; however, initial treatment (standard or otherwise) and age were not. When using both screening instruments separately, an impaired score on the G8 and higher disease stage were the variables remaining in the regression analyses (HR for impaired G8, 3.01; 95% CI, 1.35-6.72; P < .001). Patients with impaired scores on the ISAR-HP and G8 had more geriatric impairments than did patients with only an impaired G8 score. Conclusion: G8 screening is useful for the prognostication of elderly patients with lung cancer and could be used in combination with ISAR-HP to increase specificity at the cost of sensitivity. Using the ISAR-HP as the only screening tool would be insufficient.

Decision-making for older patients with lung cancer can be complex and challenging. A geriatric assessment (GA) may be helpful and is increasingly being used since 2005 when SIOG advised to incorporate this in standard work-up for the elderly with cancer. Our aim was to evaluate the value of a geriatric assessment in decision-making for patients with lung cancer.Between January 2014 and April 2016, data on patients with lung cancer from two teaching hospitals in the Netherlands were entered in a prospective database. Outcome of geriatric assessment, non-oncologic interventions, and suggested adaptations of oncologic treatment proposals were evaluated.83 patients (median age 79 years) were analyzed with a geriatric assessment, of which 59% were treated with a curative intent. Half of the patients were classified as ECOG PS 0 or 1. The majority of the patients (78%) suffered from geriatric impairments and 43% (n = 35) of the patients suffered from three or more geriatric impairments (out of eight analyzed domains). Nutritional status was most frequently impaired (52%). Previously undiagnosed impairments were identified in 58% of the patients, and non-oncologic interventions were advised for 43%. For 33% of patients, adaptations of the oncologic treatment were proposed. Patients with higher number of geriatric impairments more often were advised a reduced or less intensive treatment (p < 0.001).A geriatric assessment uncovers previously unknown health impairments and provides important guidance for tailored treatment decisions in patients with lung cancer. More research on GA-stratified treatment decisions is needed.

Background and purpose Radiation dose escalation using hypofractionation might improve overall survival (OS). We investigated OS in a phase II multicenter study in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with hypofractionated concurrent chemoradiotherapy. Materials and methods A 2-armed phase II, multi-center study (NTR2230) was performed with the aim to assess the effect of cetuximab to concurrent chemoradiotherapy in LA-NSCLC patients (stage II/IIIA/B). Arm A received high dose radiotherapy (24×2.75Gy) and concurrent daily low-dose cisplatin (6mg/m2). Arm B received an identical treatment regimen with additional weekly cetuximab. Kaplan–Meier survival curves and 1-, 2- and 5-year OS proportions were calculated. Results Between February 2009 and May 2011, 102 patients were randomly allocated in two arms. Median OS was 31.5months (range 12.8–52.3), not significantly different between arms A and B; 33.0 (range 17.0–57.0) and 30.0 (11.0–52.0) months. 1-, 2- and 5-year OS rates were 74.5%, 59.4% and 37.3%, respectively. In multivariate analyses, worse performance score, V35 of the esophagus and the existence of comorbidities were significantly (P-value<0.05) associated with a shorter OS. Discussion In this phase II trial, the median OS for the entire group was remarkably high; 31.5months. Furthermore, 5-year OS was still 37.3%. Hypofractionation might contribute to improved OS in LA-NSCLC patients.

8089 Background: NTG increases tumor blood flow and thereby may augment drug delivery to the tumor and inhibits HIF-1a, a major regulator of hypoxia. In mouse models addition of HIF-1α inhibitors to B significantly impairs tumor growth. A randomized phase II study has shown improved clinical outcome when NTG patches were added to vinorelbine/cisplatin in pts with advanced NSCLC (Yasuda, 2006). We hypothesized that adding NTG to PCB improves progression free survival (PFS), response rate (RR) and overall survival (OS) in pts with stage IV non-squamous NSCLC. Methods: This open-label multicenter phase II trial randomized chemo-naive pts with stage IV non-squamous NSCLC 1:1 to PCB with or without NTG. Main other inclusion criteria: performance score 0-2; measurable disease (RECIST 1.1); adequate bone marrow, liver and renal function; written informed consent; no clinical significant cardiovascular disorders; no significant bleeding. Pts were treated with P 200 mg/m2 day (d) 1-C AUC 6 d1-B 15 mg/kg d1 every 3 weeks (wks) without (Arm A) or with (Arm B) NTG 15 mg/24 h for 5 d (d -2 to +3) every cycle for 4 cycles and B and NTG until progression. Tumor measurements were assessed every 2 cycles. The study was powered (80%) to detect a decrease in the hazard of progression of 33% in arm B at α = 0.05 with a two-sided log rank test when 222 pts were enrolled and followed until 195 events were observed. Results: Between 01-2011 and 01-2013 223 pts were randomized; 112 arm A and 111 arm B; 50% males; median (range) age 62 years (39-81); 85% adenocarcinoma. Pts characteristics were balanced between both arms. RR was 45% in arm A and 30% in arm B. Median (95% CI) PFS in arm A was 6.8 months (m) (5.6-7.3) and 5.0 m (4.2-5.8) in arm B, HR 1.22 (95% CI 0.91-1.63). OS was 11.6 m (8.7-14) in arm A and 9.5 m (7.8-11.9) in arm B, HR 1.12 (95% CI 0.76-1.67). In arm B no additional toxicity was observed except headache (14% arm A and 57% arm B). Conclusions: Adding NTG to first line PCB does not improve PFS and OS in pts with stage IV non-squamous NSCLC. No further study with this regimen is warranted. Clinical trial information: NCT01171170.

BackgroundModest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab.Patients and methodsPatients received high dose accelerated radiotherapy (66Gy in 24 fractions) and concurrent daily Cisplatin (6mg/m2) without (Arm A) or with (Arm B) weekly Cetuximab (400mg/m2 loading dose one week prior to radiotherapy followed by weekly 250mg/m2). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6–8weeks after treatment. Toxicity was reported as well.ResultsBetween February 2009 and May 2011, 102 patients were randomized. Median follow up was 29months. The OLCR was 84% in Arm A and 92% in Arm B (p=0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p=0.39; OS p=0.99). Toxicity compared equally between both groups.ConclusionThe addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity.