Metastatic Non-squamous Non-small Cell Lung Research Articles

Pharmacoeconomic evaluation of first-line combination therapy with immunotherapy drugs and platinum-containing chemotherapy in adult patients with metastatic non-squamous non-small cell lung cancer

Objective: to evaluate the pharmacoeconomic efficacy of “atezolizumab + bevacizumab + paclitaxel + carboplatin” drug combination compared to “pembrolizumab + pemetrexed + carboplatin” combination in adult patients with non-small cell lung cancer (NSCLC) in the first line of therapy.Material and methods. The modeling was applied for cost minimization analyzis of using compared therapy regimens with comparable efficacy, and to estimate the impact on the healthcare budget when increasing the proportion of patients in the target population receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination. Published adjusted indirect comparison data were used in modeling. The calculations were based on the registered prices according to the state register of maximum selling prices.Results. The use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination instead of “pembrolizumab + pemetrexed + carboplatin” combination will decrease the direct medical costs of therapy per 1 patient for 2 years by 28,165.00 rubles (–0.4%). The budget impact analysis showed that an increase in the proportion of patients receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination from 50% (current therapy practice) to 100% (considered therapy practice) will reduce the budget load for the population of 6,240 patients over 2 years by 256.1 million rubles (–0.64%).Conclusion. The results of pharmacoeconomic analysis demonstrated that the use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination in first-line therapy for metastatic NSCLC is economically feasible and reduces the load on the budget compared to “pembrolizu- mab + pemetrexed + carboplatin” scheme.

Abstract LB107: Association of circulating free DNA (cfDNA) maximum variant allele frequency (mVAF) levels with clinical outcomes in patients (pts) with metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with pembrolizumab (pembro) + chemotherapy (chemo) in the phase 2 KEYNOTE-782 trial

Abstract Background: The phase 2 KEYNOTE-782 trial (NCT03664024) was designed to prospectively evaluate plasma-derived biomarkers of response to first-line pembro + chemo in pts with metastatic nonsquamous NSCLC. This exploratory analysis of KEYNOTE-782 evaluated the association of cfDNA mVAF levels with clinical outcomes. Methods: Adults with untreated stage IV nonsquamous NSCLC received pembro 200 mg Q3W + chemo (pemetrexed + carboplatin or cisplatin). cfDNA was isolated from plasma samples collected at baseline (BL) and cycle 2 (C2) and sequenced using a targeted NGS-based assay previously used to assess blood tumor mutational burden from cfDNA for the primary analysis. cfDNA mVAF was quantified for each patient. The associations of BL cfDNA mVAF (all pts) and change in cfDNA mVAF from BL at C2 (pts with ≥1 detectable variant at BL; cfDNA+) as continuous variables with ORR, PFS, and OS were evaluated; 1-sided α was prespecified at 0.05 after multiplicity adjustment. ORR, PFS, and OS were also descriptively evaluated by cfDNA bins (BL mVAF, >0 vs 0; mVAF change from BL, ≥median vs <median). Results: Of 101 pts with evaluable cfDNA samples at BL, 83 (82.2%) were cfDNA+; 74 of these 83 pts had evaluable cfDNA samples at C2. Low BL mVAF was associated with improved ORR, PFS, and OS (P <0.01, each). The area under the receiver operating characteristic curve (AUROC) for discriminating response was 0.61 (95% CI, 0.50-0.72). Among pts with BL mVAF >0 (n = 83) vs 0 (n = 18), ORR (95% CI) was 38.6% (28.1-49.9) vs 55.6% (30.8-78.5), median PFS (95% CI) was 6.6 mo (4.9-9.0) vs 19.7 mo (9.8-not reached [NR]), and median OS (95% CI) was 13.6 mo (9.4-22.5) vs 31.6 mo (20.1-NR). Larger reductions in mVAF from BL at C2 were associated with improved ORR, PFS, and OS (P <0.05, each). The AUROC for discriminating response was 0.69 (95% CI, 0.57-0.82). After adjustment for best overall response, change in mVAF from BL at C2 was not associated with PFS or OS (P >0.05). In a descriptive evaluation for pts with a mVAF change from BL at C2 ≥median of 0.15 (n = 37) vs <median (n="37)," orr="" (95%="" ci)="" was="" 18.9%="" (8.0-35.2)="" vs="" 64.9%="" (47.5-79.8),="" median="" pfs="" 5.1="" mo="" (4.2-11.1)="" 7.2="" (6.2-21.7),="" and="" os="" 12.8="" (7.9-18.1)="" 25.9="" (15.3-nr).="" conclusions:="" in="" pts="" with metastatic nonsquamous NSCLC treated with pembro + chemo, low cfDNA mVAF levels at BL and larger reductions in cfDNA mVAF levels were associated with improved clinical outcomes. However, after correction for clinical response, the prognostic value of cfDNA mVAF reduction was not significant. Further studies are warranted to elucidate the utility of cfDNA for disease monitoring in this setting. Citation Format: Jair Bar, Emilio Esteban, Delvys Rodríguez-Abreu, Santiago Ponce-Aix, Zsuzsanna Szalai, Enriqueta Felip, Maya Gottfried, Mariano Provencio Pulla, Andrew Robinson, Andrea Fülöp, Suman Bannur Rao, D. Ross Camidge, Giovanna Speranza, Nathan Hunkapiller, Robert McDaniel, Byoungsok Jung, David Burkhardt, Ruth Mauntz, Cai Chen, Carol Pena, Razvan Cristescu, Elisha J. Dettman, Steven M. Townson, Julie Kobie, Tibor Csőszi. Association of circulating free DNA (cfDNA) maximum variant allele frequency (mVAF) levels with clinical outcomes in patients (pts) with metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with pembrolizumab (pembro) + chemotherapy (chemo) in the phase 2 KEYNOTE-782 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB107.

Abstract CT284: A phase 3 randomized controlled trial of zongertinib (BI 1810631) compared with standard of care in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations: Beamion LUNG-2

Abstract Background: First-line (1L) standard of care for patients with HER2 mutation-positive (HER2m+) non-small cell lung cancer (NSCLC) is platinum-based chemotherapy ± immunotherapy. To date, no targeted 1L treatments have been approved. Zongertinib is a HER2-selective tyrosine kinase inhibitor that binds to wild-type and mutated HER2, and spares EGFR. In Phase Ia of Beamion LUNG-1 (NCT04886804), zongertinib conferred objective response/disease control rates of 49/91% in patients with pretreated HER2 aberration-positive solid tumors, and 58/97% in those patients with HERm+ NSCLC, with manageable safety with few EGFR-associated adverse events. Purpose: Here we describe Beamion LUNG-2 (NCT06151574), a phase 3, randomized, controlled, open-label trial that will compare the efficacy and safety of 1L zongertinib with standard of care in patients with HER2m+, locally advanced/metastatic nonsquamous NSCLC. Experimental design: Approximately 270 patients will be randomized 1:1 to receive either zongertinib or standard of care. Key inclusion criteria: histologically/cytologically diagnosed advanced/metastatic nonsquamous NSCLC; no prior systemic treatment for locally advanced/metastatic disease; HER2 mutation in the tyrosine kinase domain; ≥1 measurable lesion (RECIST 1.1). Key exclusion criteria: tumors that have alterations with available therapy, and radiotherapy/major surgery ≤4 weeks prior to randomization. In the experimental arm, oral zongertinib 120 mg once daily will be given in 21-day cycles. In the comparator arm, intravenous pemetrexed 500 mg/m2 chemotherapy plus either cisplatin 75 mg/m2 or carboplatin area under the curve 5, plus pembrolizumab 200 mg will be given on day 1 every 3 weeks for 4 cycles, followed by pemetrexed 500 mg/m2 plus pembrolizumab 200 mg every 3 weeks for ≤35 cycles. In both arms, treatment will continue until progressive disease (RECIST 1.1), undue toxicity, or other criteria are met. Primary endpoint: progression-free survival (RECIST 1.1). Secondary endpoints: overall response (defined as best overall response of complete or partial response, RECIST 1.1), patient-reported outcomes (changes from baseline to Week 25), overall survival, and adverse events during the on-treatment period (CTCAE 5.0). Citation Format: Yi-Long Wu, Melissa Johnson, Ross Soo, Navid Baktash, Daniela Maier, Sabina Eigenbrod-Giese, Tatsuya Yoshida. A phase 3 randomized controlled trial of zongertinib (BI 1810631) compared with standard of care in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations: Beamion LUNG-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT284.

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL).

The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program. PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability. Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate. The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily.

102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

Cost-Effectiveness Analysis of Sintilimab Plus Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer: A Societal Perspective.

The updated ORIENT-11 study demonstrated that sintilimab, when combined with chemotherapy, had promising survival advantage compared to standard chemotherapy alone in the first-line treatment for previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (nsNSCLC). This study aims to evaluate the cost-effectiveness of sintilimab plus chemotherapy for advanced nsNSCLC from a Chinese societal perspective. A partitioned survival model with aembedded decision tree was developed to assess the economic value of sintilimab plus chemotherapy over a lifetime horizon. Clinical data was captured from the updated ORIENT-11 study, while costs, health productivity losses, and utility values were collected from a nationwide cross-sectional survey in tertiary hospitals across multiple provinces in China. The primary outcomes were measured using the metrics of quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Costs and health outcomes were discounted at an annual rate of 5% per annum. Sensitivity analyses, including one-way and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses, were performed. Compared to standard chemotherapy, treatment with sintilimab plus chemotherapy incurred a mean total cost of $23,979 and gained 0.98QALYs over the lifetime horizon, resulting in an ICER of $24,568 per QALY gained. The use of sintilimab accumulated direct non-medical costs of $9262 and indirect costs of $6780 over 16years. Probabilistic sensitivity analyses showed an 84.2% probability of sintilimab plus chemotherapy being cost-effective at a threshold of three times China's per capita gross domestic product in 2022 ($38,201). The model was most sensitive to the discount rate of QALYs and costs, as well as the costs of pemetrexed, sintilimab, and subsequent therapy in progressive disease state. Subgroup analyses indicated favorable incremental net monetary benefits in all subgroups. Sintilimab plus chemotherapy is a cost-effective first-line treatment therapy for advanced nsNSCLC in China when compared to standard chemotherapy. These findings, along with the improved progression-free survival and overall survival (OS)observed in ORIENT-11, support the use of this regimen in eligible candidates for advanced nsNSCLC.

Prevalence of asymptomatic brain metastases in metastatic nonsquamous nonsmall cell lung cancer: Treatment implications for resource-constrained settings

Abstract Background: Brain metastases (BM) are common in metastatic nonsmall cell lung cancer (NSCLC). However, routine neuroimaging in asymptomatic patients with metastatic NSCLC is controversial as there is no conclusive evidence of benefit from the detection and treatment of asymptomatic BM. Herein, we evaluated the prevalence of asymptomatic BM and its treatment implications in a resource-limited setting. Methods: Consecutive patients with newly diagnosed, treatment-naïve, metastatic, nonsquamous NSCLC (NS-NSCLC) were included. Subjects who already had clinical or radiological features suggestive of BM were excluded from the study. All eligible subjects underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain. Management of the detected BM was at the discretion of the treating clinicians. Results: Among 809 subjects who were screened, 100 (12.4%) were included in the study and underwent MRI. BM was present in 30 (30%) of the subjects and absent in the remaining 70 subjects. A majority of BM were multiple (70%), involved the frontal lobe commonly (73.3%), and had a mean (standard deviation) size of 13.2 (7.3) mm. Detection of BM resulted in a treatment alteration in 17 (17%) of the study subjects (brain irradiation, n = 17, change in targeted therapy, n = 3) with BM. There was no difference in survival of patients who underwent treatment alteration for management of BM compared to those who did not (P = 0.132). Conclusions: About one-third of patients with metastatic NS-NSCLC had BM in MRI despite the absence of symptoms. Despite treatment of the majority of the patients with BM with brain irradiation, there was no demonstrable survival benefit. Hence, we conclude that although routine neuroimaging of asymptomatic patients with newly diagnosed metastatic NSCLC may result in treatment alteration (primarily brain irradiation) in a small proportion of patients, it may not influence outcomes in resource-constrained settings.

OP11 Cost-Effectiveness Of Atezolizumab Plus Chemotherapy As A First-Line Treatment For Metastatic Non-Squamous Non-Small Cell Lung Cancer

IntroductionTreatment with atezolizumab plus standard chemotherapy can prolong the overall survival of patients with metastatic non-squamous non-small cell lung cancer (NSCLC). However, the economic value of this treatment regimen is unknown. This study aimed to estimate the cost effectiveness of atezolizumab plus chemotherapy in the first-line treatment of metastatic non-squamous NSCLC from a healthcare system perspective in China.MethodsA partitioned survival model consisting of three discrete health states was developed to estimate the cost and effectiveness of atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) versus carboplatin or cisplatin plus pemetrexed (PP) in the first-line treatment of metastatic non-squamous NSCLC over a 12-year lifetime horizon. Key clinical data were generated from the IMpower132 trial. Local direct medical and non-medical costs were used and health preference data were collected from patients with NSCLC in 13 tertiary hospitals across five provinces in China. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model.ResultsCompared with the PP regimen, APP therapy yielded a gain of 0.21 QALYs at an increased cost of CNY145,602 (USD22,574), resulting in an ICER of CNY684,894 (USD106,185) per QALY gained. The ICER was significantly higher than three times the gross domestic product per capita for China in 2021 (USD37,663). One-way sensitivity analyses revealed that one of the most influential factors in this model was the cost of atezolizumab. Probabilistic sensitivity analysis showed that there was 14.7% probability that atezolizumab plus chemotherapy was cost effective at a willingness-to-pay value of CNY242,928 (USD37,663) per QALY gained.ConclusionsThe APP regimen could prolong survival and improve health benefits over standard chemotherapy in the first-line treatment of patients with metastatic non-squamous NSCLC, but it is unlikely to be a cost-effective treatment option in China.

81P Real-world experience with docetaxel regimens in metastatic non-squamous (mNSq) non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy (PCT) and an immune checkpoint inhibitor (ICI) in the United States (US)

81P Real-world experience with docetaxel regimens in metastatic non-squamous (mNSq) non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy (PCT) and an immune checkpoint inhibitor (ICI) in the United States (US)

Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial

PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m2 pemetrexed and ≤4 cycles cisplatin (75 mg/m2) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4–54.8) for DCT and 39% (48/122; 30.6–48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7–10.4) for DCT and 6.7 (4.9–7.1) for PCT (HR 0.70 [95% CI: 0.50–0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5–NR) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.53–1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC.

LBA13 Dostarlimab + chemotherapy (CT) vs pembrolizumab + CT in metastatic non-squamous non-small cell lung cancer (NSCLC): Updated Asian subgroup analyses of the PERLA trial

LBA13 Dostarlimab + chemotherapy (CT) vs pembrolizumab + CT in metastatic non-squamous non-small cell lung cancer (NSCLC): Updated Asian subgroup analyses of the PERLA trial

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

The Cost-Effectiveness of Sugemalimab Plus Chemotherapy as First-Line Treatment for Metastatic Squamous and Non-squamous NSCLC in China.

Sugemalimab is the first China-developed programmed death-ligand 1 inhibitor that has proved to be effective as a first-line treatment for both metastatic squamous and non-squamous non-small cell lung cancer (NSCLC) when used in combination with chemotherapy. This study compared the cost-effectiveness of sugemalimab plus chemotherapy (sugema + chemo) with placebo plus chemotherapy (placebo + chemo) among metastatic squamous and nonsquamous NSCLC, respectively. Separate Markov models were constructed to generate the cumulative healthcare costs and quality-adjusted life-years (QALYs) associated with two treatment strategies over a 20-year time horizon. Transition probabilities were estimated using survival data reported in the GEMSTONE-302 trial. Health state utilities and costs were derived from published literature, national databases, and local general hospitals. Sensitivity analyses were performed to test the robustness of our conclusions. Compared with first-line placebo + chem, sugema + chemo achieved an incremental cost-effectiveness ratio (ICER) of $57,842/QALY for patients with metastatic squamous NSCLC and achieved an ICER of $78,249/QALY for patients with metastatic non-squamous NSCLC. In our sensitivity analyses of a willingness-to-pay (WTP) threshold of $35,663 per QALY, the first-line sugema + chemo was only cost-effective for patient groups when the price of sugemalimab decreased. Sugema + chemo was not cost-effective as a first-line treatment for either metastatic squamous or metastatic nonsquamous NSCLC in Chinese patients compared with placebo + chemo. However, we found that sugema + chemo would be cost-effective in patients withmetastatic squamous and non-squamous NSCLC when sugemalimab's price was decreased by > 39.0% and 64.8%, respectively.

Phase 1b/2a safety and tolerability study of bemcentinib (BEM) with pembrolizumab/carboplatin/pemetrexed in first line (1L) advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without/with a STK11 mutation.

TPS9154 Background: The combination of platinum, pemetrexed, and pembrolizumab (CIT) has become the standard of care in 1L non–oncogene addicted NSCLC. Despite an initial improvement in response rate and survival, the 5-year survival of NSCLC remains approximately 20-30%, due to the emergence of primary and acquired resistance. Additionally, the presence of brain metastases occurs in ˜30-50% of NSCLC patients and confers a poor prognosis. Among the currently non-actionable mutations, STK11/LKB1 mutations (STK11m) are common (˜20%) in NSCLC. Recent evidence suggests that STK11m NSCLC patients have a minimal response to checkpoint inhibitors and to chemo-immunotherapy in the first line setting. STK11m tumors are characterized by an immune-suppressed phenotype which is highly associated with AXL signalling. BEM, a first-in-class, oral, selective AXL inhibitor, has demonstrated the ability to prevent chemoresistance, re-sensitize STK11m NSCLC tumors to pembrolizumab, and enhance efficacy of CIT in preclinical lung models. Moreover, following oral administration, BEM readily distributes in brain tumour tissue in recurrent glioblastoma patients, with a 25.9 mean ratio of drug concentration in brain tissue to plasma. Therefore, the addition of BEM to CIT has the potential to improve 1L treatment outcomes in NSCLC overall and particularly in STK11m tumors. Methods: This is an open-label, multi-center, phase 1b/2a study to assess the safety, tolerability, and preliminary anti-tumor activity of BEM + CIT as 1L treatment in patients with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC without actionable mutations. Patients with stable brain metastases are eligible to participate. Phase 1b follows a 3+3 design and will explore CIT in combination with one of 3 BEM dose levels: Cohort 1 = 75mg; Cohort 2 = 100 mg; or Cohort 3 = 150 mg. BEM is administered orally once/day on Day 1 of each 21-day treatment cycle. After 4 cycles of CIT + BEM, maintenance with BEM + pemetrexed + pembrolizumab is administered for up to 2 years. An independent data safety monitoring board will assess the safety data at the end of the dose-limiting toxicity period (the first 21 days of treatment for each patient, i.e. cycle 1) of each cohort and will recommend the BEM dose for the phase 2a expansion. In the phase 2a, up to 40 patients harboring a STK11m (regardless of their co-mutational status), in the absence of driver mutations will be enrolled. The study will include extensive co-mutational analyses via next-generation sequencing to identify potential sub-groups of patients deriving particular benefit. The trial is open to patient enrolment in phase1b in the US; recruitment for phase 2a is planned to open in Q2 2023 in Europe and US. EudraCT 2019‐003806‐28/NA/124645. Clinical trial information: NCT05469178 .

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab.

9099 Background: PERLA (NCT04581824) is a global, randomized, Phase II, double-blind study assessing the efficacy and safety of chemotherapy (CT) combined with programmed death 1 (PD-1) inhibitors dostarlimab (dostCT) and pembrolizumab (pembCT) as first-line (1L) treatment (tx) for patients (pts) with metastatic non-oncogene-driven, non-squamous, NSCLC. DostCT had similar efficacy and safety to pembCT [1]. Exploratory analyses of patient-reported outcomes (PROs) from PERLA have been conducted. Methods: In PERLA, pts with ECOG status 0–1 were randomized 1:1 to receive ≤35 cycles (C) of dostCT or pembCT Q3W (CT was ≤35 cycles [C] of 500 mg/m2 pemetrexed every 3 weeks [Q3W] and ≤4C of cisplatin or carboplatin). PROs were collected at baseline (BL), Q3W until C4, Q9W until C16, Q12W until end of tx and at 30-day safety follow-up. Change from BL in EORTC QLQ-C30 &amp; QLQ-LC13 were analyzed using a longitudinal mixed model, with a ≥10-point change from BL considered clinically meaningful; scores were categorized as improved, stable, or worsened. Time to deterioration (TTD) in QLQ-C30 and selected QLQ-LC13 symptoms were estimated using Kaplan–Meier methods. Results: Analysis populations for dostCT/pembCT included 102/99 pts for QLQ-C30 and 96/90 pts for QLQ-LC13. Completion rates for QLQ-C30 and QLQ-LC13 were &gt;80% up to C4 in both tx arms, decreasing after C7. At C13, 55.0% [n=33/60] and 54.2% [n=32/59] of dostCT pts, and 37.1% [n=23/62] and 35.7% [n=20/56] of pembCT pts completed QLQ-C30 and QLQ-LC13, respectively. Overall, least squares (LS) mean QLQ-C30 and QLQ-LC13 scores remained stable up to C13. Relative to BL, average pt functioning (e.g., physical, role) and cancer symptoms (e.g., pain, cough, dyspnea) were stable through C13 (~1 yr on tx); no clinically meaningful difference in LS mean QLQ-C30 or QLQ-LC13 scores were observed between tx arms. Across most QLQ-C30 and QLQ-LC13 subscales, &gt;60% pts in both tx arms had stable or improved responses up to C13. At C13, meaningful improvements in chest pain and dyspnea were reported in a higher % of dostCT pts (34.4% [n=11/32] and 40.6% [n=13/32], respectively) than pembCT pts (10.0% [n=2/20] and 25.0% [n=5/20], respectively). TTD for QLQ-C30 and QLQ-LC13 subscales were comparable between tx arms, except for longer median TTD in dyspnea in dostCT pts (N=96) than pembCT pts (N=90) (4.24 vs 1.54 months; HR 0.64 [95% CI: 0.44–0.93]). Conclusions: HRQoL was similar and stable through C13 in both tx arms. These results supplement efficacy and safety data reported in PERLA and support further investigation of dostarlimab as an appropriate PD-1 inhibitor for use in combination with standard of care and novel therapies in metastatic NSCLC.

First-line pembrolizumab plus platinum-pemetrexed in metastatic non-small cell lung cancer: Clinical experience in a Spanish tertiary hospital.

e21142 Background: In the phase III trial KEYNOTE-189 first-line pembrolizumab (pembro) plus platinum-pemetrexed (pem) significantly improved OS and PFS in metastatic nonsquamous non-small cell lung cancer (NSCLC) without EGFR/ALK alterations. We report outcomes of real-world patients (pts) treated with first line pembro plus platinum-pem in our hospital. Methods: We have done a descriptive, retrospective, single center study developed in a Spanish tertiary hospital where patients with metastatic nonsquamous NSCLC treated with first-line pembro plus platinum-pem have been included. SPSS v23 software has been used to analyze clinical data for OS and PFS using the Kaplan-Meier method. PFS-2, defined as time from first treatment to objective tumor progression on next-line treatment or death from any cause, whichever occurred first, was also recorded using the Kaplan-Meier method. Adverse events (AEs) were graded according to CTCAE v5.0. Results: From December 2019 to May 2022, 79 pts (67.1% M, 26% W; 64y median age, ECOG 0, 1, 2: 5.1%; 88.6% and 6.3%; PD-L1 &lt; 1% 36 [45.6%], PD-L1 1-49% 37 [36.8%], PD-L1 50% 3 [3.8%]; unknown PD-L1 3 [3.8%]; 95% adenocarcinoma) were assessed. After a median follow-up of 19 months, OS was 17 months (5.3-28.7). Stratified by PD-L1 expression, mOS was 9 months (6.3 -11.7) in PD-L1 &lt; 1%; 25 months in PD-L1 1-49%, NR in the rest. Median PFS was 9 months (5.8-12.2). According to PD-L1 expression, mPFS was 6 months (4.6 - 7.4) in PD-L1 &lt; 1%; 19 months (8.7 - 29.2) PD-L1 1-49% and 7 months (0.6 - 13.4) in PD-L1 50%. PFS-2 was 17 months (10.7 - 23.3). At the time of the cut off 66 pts (83.5%) had discontinued treatment: 35 (53%) due to progression, 23 (34.8%) due to toxicity; 2 (3%) due to both, and 6 (9.1%) due to other reasons. Grade 3-5 AEs were observed in 35/79 pts (44.3%). 15.2% pts needed dose-reduction and 32.6% glucocorticoids. Conclusions: First-line treatment with pembro plus platinum-pem has demonstrated benefit in terms of OS, PFS and PFS-2 with tolerable adverse effects. The results obtained in our hospital, taken together, are consistent with those published in KEYNOTE-189 trial. However, the survival of our pts with PD-L1 &lt; 1% seems to be poorer. This finding could be explained by the short median follow-up, low number of patients and differences in baseline demographic characteristics.

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer.

The detection of ROS1 rearrangements in metastatic non-squamous non-small cell lung carcinoma (NS-NSCLC) permits administration of efficient targeted therapy. Detection is based on a testing algorithm associated with ROS1 immunohistochemistry (IHC) screening followed by ROS1 FISH and/or next generation sequencing (NGS) to confirm positivity. However, (i) ROS1 rearrangements are rare (1-2% of NS-NSCLC), (ii) the specificity of ROS1 IHC is not optimal, and (iii) ROS1 FISH is not widely available, making this algorithm challenging to interpret time-consuming. We evaluated RNA NGS, which was used as reflex testing for ROS1 rearrangements in NS-NSCLC with the aim of replacing ROS1 IHC as a screening method. ROS1 IHC and RNA NGS were prospectively performed in 810 NS-NSCLC. Positive results were analyzed by ROS1 FISH. ROS1 IHC was positive in 36/810 (4.4%) cases that showed variable staining intensity while NGS detected ROS1 rearrangements in 16/810 (1.9%) cases. ROS1 FISH was positive in 15/810 (1.8%) of ROS1 IHC positive cases and in all positive ROS1 NGS cases. Obtaining both ROS1 IHC and ROS1 FISH reports took an average of 6 days, while obtaining ROS1 IHC and RNA NGS reports took an average of 3 days. These results showed that systematic screening for the ROS1 status using IHC must be replaced by NGS reflex testing.

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

44P Dostarlimab (Dos) or pembrolizumab (Pem) + chemotherapy (CT) in previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC): Patient (Pt) and disease characteristics subgroup analyses from the PERLA trial

44P Dostarlimab (Dos) or pembrolizumab (Pem) + chemotherapy (CT) in previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC): Patient (Pt) and disease characteristics subgroup analyses from the PERLA trial

Comparing the cost-effectiveness of sintilimab + pemetrexed plus platinum and pemetrexed plus platinum alone as a first-line therapy for Chinese patients with nonsquamous non-small cell lung cancer.

Pemetrexed plus platinum alone is the conventional first-line therapy for locally advanced metastatic nonsquamous non-small cell lung cancer (NSCLC) without targetable genetic aberrations. The ORIENT-11 trial revealed that sintilimab + pemetrexed plus platinum could yield more survival benefits for patients with nonsquamous NSCLC. The present study aimed to assess the cost-effectiveness of sintilimab + pemetrexed plus platinum vs. that of pemetrexed plus platinum alone as the first-line therapy for patients with nonsquamous NSCLC to inform clinically rational drug use and provide a basis for medical decision-making. A partitioned survival model was created to evaluate the cost-effectiveness of two groups from the perspective of the healthcare system in China. The clinical data for adverse event probabilities and extrapolating long-term survival originally collected in a phase III clinical trial (ORIENT-11) were retrieved. Local public databases and literature were used to acquire data on utility and cost. The heemod package in R software was used to calculate the life years (LYs), quality-adjusted LYs (QALYs), and total costs in each group to generate the incremental cost-effectiveness ratio (ICER) in the base case and to conduct deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA). Our base case analysis (BCA) revealed that sintilimab combined with pemetrexed plus platinum provided an increase of 0.86 in QALYs with an increasing cost of United State dollar (USD) $4,317.84 relative to pemetrexed plus platinum in Chinese patients with nonsquamous NSCLC who were negative for targetable genetic variations, which induced an ICER of USD $5,020.74/QALY. The ICER value was lower than the set threshold value. The results exhibited strong robustness in the sensitivity analysis. In DSA, the parameter for the overall survival (OS) curve in chemotherapy and the cost of best supportive care were the main factors that impacted the result of the ICER. The PSA indicated that sintilimab and chemotherapy combination therapy was cost-effective. This study suggests that the combination of sintilimab + pemetrexed plus platinum is cost-effective as a first-line therapy in Chinese patients with nonsquamous NSCLC who are negative for targetable genetic variations from the perspective of the healthcare system.