High Non-small Cell Lung Cancer Research Articles

EPH193 The Role of Adjuvant Atezolizumab in Reducing Recurrence-Related Treatment Costs in Resected Early-Stage PD-L1 High Non-Small Cell Lung Cancer across Europe

EPH193 The Role of Adjuvant Atezolizumab in Reducing Recurrence-Related Treatment Costs in Resected Early-Stage PD-L1 High Non-Small Cell Lung Cancer across Europe

Estimating the impact of adjuvant atezolizumab in preventing recurrences and reducing costs in resectable early PD-L1 high non-small cell lung cancer in Europe.

e20501 Background: Recurrences of non-small cell lung cancer (NSCLC) after surgery remain common and are associated with significant morbidity and mortality. Loco-regional or metastatic disease recurrence can lead to a substantial health care resource use and economic burden. The aim of this study was to estimate the effect of treating patients with early-stage NSCLC with adjuvant atezolizumab (ATZ) on the number of recurrences and direct healthcare costs in Germany, Spain, France Italy and the UK, together referred to as EU5. Methods: Using an epidemiological model, we estimated the reduction in loco-regional (LR) recurrences or distant metastases (DM) after adjuvant ATZ treatment following chemotherapy in operable NSCLC patients with PDL-1 expression of ≥ 50% on tumor cells (PD-L1 high), stage II-IIIA (AJCC 7th edition staging), without EFGR or ALK alterations. We used data from cancer registries, published literature sources, and market research to obtain incidence rates, staging distribution, biomarker status data, and adjuvant treatment rates. Moreover, we used evidence on the disease-free survival (DFS) of patients on adjuvant ATZ from the IMpower010 (NCT02486718) clinical trial to calculate the projected reduction in the number of LR recurrences or DM over a 10-year period post-ATZ launch relative to best supportive care (BSC). The model considers the costs associated with treatment, management of adverse events, monitoring of the disease, and follow-up healthcare. Results: We project that between 2023 and 2033, 20,483 patients with resected PD-L1 high stage II-IIIA NSCLC would experience recurrence (LR, or DM, or both) in the EU5 if they were treated with BSC (adjuvant platinum-based chemotherapy) alone (Table 1). Assuming peak ATZ uptake of 75%, the model estimates that following adjuvant ATZ and chemotherapy, a total of 4,665 recurrences would be prevented in this patient population in the EU5 over 10 years, representing a 23% decrease in recurrence relative to BSC. These avoided recurrences in EU5 could translate into a considerable reduction in direct healthcare costs. Conclusions: Adjuvant ATZ following chemotherapy results in a considerable population-level reduction of loco-regional recurrence or distant metastasis in resected PD-L1 high stage II-IIIA NSCLC patients. This could translate into a substantial decrease in the economic and societal burden caused by the disease. [Table: see text]

EPH19 Long Term Epidemiological Impact of Adjuvant Atezolizumab in Preventing the Recurrence of Early PDL1 High Non-Small Cell Lung Cancer in Europe

To estimate the impact of adjuvant Atezolizumab (ATZ) in preventing the recurrence of early non-small cell lung cancer (eNSCLC) in 5 European countries (EU5).

113P Comparative efficacy and safety of PD-1/PD-L1 inhibitor monotherapy or in addition to chemotherapy for advanced, PD-L1 high non-small cell lung cancer (NSCLC): A meta-analysis of randomized trials

Background: PD-(L)1 inhibitors, alone and in association with chemotherapy (CT), improved the outcomes of advanced, PD-L1 high non-small cell lung cancer (NSCLC) patients as compared to CT alone. Nonetheless, no direct comparison exists between these agents.

P1.16-10 Real-World Efficacy of First-Line Pembrolizumab in Patients with Advanced PD-L1 High Non-Small Cell Lung Cancer in Argentina

Pembrolizumab monotherapy is a standard first-line (1L) treatment regimen for patients (pts) with non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. We aimed to study the clinical efficacy and toxicity of this approach in the real-world setting in Argentina. We conducted a retrospective, multicenter study. Patients with metastatic NSCLC and a PD-L1 TPS ≥ 50% treated in 1L with at least one dose of pembrolizumab monotherapy, from December 2016 to February 2019, were included. Data was collected from clinical records, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were estimated. Cox regression model was performed for uni- and multivariate analysis. A total of 53 pts were included. Median age (range) was 68 years (35-88), 33 (62.3%) were male, and 46 pts (86.7%) were smokers. Most tumors were lung adenocarcinoma (N=47, 88.7%), median (IQR) PD-L1 TPS was 79% (60-87.5) and 22 tumors (41.5%) had a TPS ≥75%. EGFR/ALK/ROS1 mutations/fusions were not detected. Brain (N=10; 18.9%), liver (N=5 (9.4%) and bone (N=15; 28.3%) metastasis were present at baseline. Performance status (PS) score was 0-1 in 46 pts (86.8%) and 7 pts (13.2%) had PS 2. Six pts received baseline corticosteroid treatment. The ORR with pembrolizumab was 41.5% (95% CI: 28.1-55.8), median PD-L1 TPS (mTPS) was significantly higher in responders (mTPS 74% vs 67%, P = 0.04). Grade ≥3 immune-related adverse events occurred in 7 pts (13.2%) and 10 (18.9%) required systemic therapy with steroids. With a median-follow up of 12.9 months (95% CI: 8.4-17.6), median PFS and median OS were not reached. The estimated percentage of patients alive and without progression at 6 and 12 months was 64.8% and 55.8%. The estimated percentage of patients alive at 6 and 12 months was 77.5% and 69.4%. Median PFS and OS for patients with PS 2 was 2.4 months (95% CI: 1.7-3.1) and 4.5 months (95% CI: 3.1-6.0), respectively. After adjusting for PS, a PDL1 TPS score ≥75% was independently associated with improved PFS in multivariate analysis [HR 0.28 (95% CI: 0.09-0.92); P = 0.03) but not with OS. PS score equal to 2 was independently associated with decreased OS [HR 4.52 (95% CI: 1.06-19.28); P = 0.04] in multivariate analysis. Pembrolizumab monotherapy is tolerable and confers durable clinical benefit for patients with tumors expressing high levels of PD-L1 in the real world clinical setting. The optimal first-line immunotherapy approach for patients with PS 2 in this setting warrants further studies.

Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab.

Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung cancer (NSCLC). However, obtaining adequate tumor tissue for molecular testing in patients with advanced disease can be challenging. Thus, an unmet medical need exists for diagnostic approaches that do not require tissue to identify patients who may benefit from immunotherapy. Here, we describe a novel, technically robust, blood-based assay to measure TMB in plasma (bTMB) that is distinct from tissue-based approaches. Using a retrospective analysis of two large randomized trials as test and validation studies, we show that bTMB reproducibly identifies patients who derive clinically significant improvements in progression-free survival from atezolizumab (an anti-PD-L1) in second-line and higher NSCLC. Collectively, our data show that high bTMB is a clinically actionable biomarker for atezolizumab in NSCLC.

Adjuvant Chemotherapy Based on the In Vitro Histoculture Drug Response Assay for Non-small Cell Lung Cancer Improves Survival

In this study, we analyzed the usefulness of adjuvant chemotherapy for non-small cell lung cancer based on the histoculture drug response assay (HDRA). From September 2001 to December 2008, 65 patients with pathologic stage II or higher non-small cell lung cancer who underwent surgery received two-cycle HDRA-based adjuvant chemotherapy. Chemosensitivity to cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and irinotecan was examined by the HDRA. All patients were classified according to the number of administered HDRA-positive drugs: the prediction-sensitive group (PSG) (n = 31) comprised patients treated with two HDRA-positive drugs and the prediction-nonsensitive group (PNSG) (n = 34) comprised those treated with a combination of one HDRA-positive and one HDRA-negative drug or two HDRA-negative drugs. The clinical outcomes of the two groups were analyzed. The overall 5-year survival rate of the PSG was 82.4%. On the other hand, that of the PNSG was 40.1%. There were significant differences between the two groups (p = 0.03). The 5-year disease-free survival rate was more favorable in the PSG than in the PNSG (PSG: 56.5%, PNSG: 30.1%, p = 0.05). Multivariate analysis showed that chemotherapy based on the HDRA was a significant prognostic factor (p = 0.03). The prognosis of patients treated with two HDRA-positive drugs was significantly better than that of those treated with one HDRA-positive drug or HDRA-negative drugs. Adjuvant chemotherapy based on the in vitro HDRA may be useful to improve survival in patients who have undergone surgery.