Advanced Non-small Cell Lung Cancer Research Articles

Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs

BackgroundOsimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It is the preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) compared to first-generation EGFR-TKIs. However, limited research has compared its clinical effectiveness with second-generation (2nd G) EGFR-TKIs.Materials and methodsThis study recruited patients diagnosed with stage IIIb-IV EGFR-mutated NSCLC who received first-line treatment with either 2nd G EGFR-TKIs (afatinib and dacomitinib) or osimertinib between April 2020 and April 2023.ResultsThe final analysis included 168 patients, of whom 113 received 2nd G EGFR-TKIs (afatinib or dacomitinib) and 55 received osimertinib. The median progression-free survival (PFS) did not differ significantly between 2nd G EGFR-TKIs and osimertinib (del 19: 17.6 months; L858R: 20.0 months vs. 28.3 months, p = 0.081). In patients with the EGFR exon 19 deletion, osimertinib conferred a longer median PFS (28.3 vs. 17.6 months, p = 0.118) and time to treatment failure (30.2 vs. 22.7 months, p = 0.722) than 2nd G EGFR-TKIs. However, the differences were not statistically significant. In patients with with the EGFR exon 19 deletion and central nervous system metastasis, the median PFS did not differ significantly between those treated with osimertinib (14.3 months) and those treated with 2nd G EGFR-TKIs (17.6 months; p = 0.881). Multivariate regression analysis revealed that the NSCLC stage was the only independent negative predictor of PFS. The treatment patterns in the second line also differed significantly between groups (p = 0.008).ConclusionsThis study found comparable effectiveness between osimertinib and 2nd G EGFR-TKIs as first-line treatment for advanced EGFR-mutated NSCLC, with only the NSCLC stage identified as a negative predictor of PFS. However, whether the different second-line treatments affect overall survival should be examined.

OA02.04 A Phase III Study of Rilertinib Versus Gefitinib as First-Line Therapy for Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC

OA02.04 A Phase III Study of Rilertinib Versus Gefitinib as First-Line Therapy for Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC

P2.10A.03 RESOLUTION: Phase II Study of Disitamab Vedotin in Combination with Tislelizumab and Bevacizumab in Patients with HER2 Alteration Advanced NSCLC

P2.10A.03 RESOLUTION: Phase II Study of Disitamab Vedotin in Combination with Tislelizumab and Bevacizumab in Patients with HER2 Alteration Advanced NSCLC

OA14.04 Efficacy and Safety of Olomorasib with Pembrolizumab + Chemotherapy as First-Line Treatment in Patients with KRAS G12C-Mutant Advanced NSCLC

OA14.04 Efficacy and Safety of Olomorasib with Pembrolizumab + Chemotherapy as First-Line Treatment in Patients with KRAS G12C-Mutant Advanced NSCLC

OA11.06 Cemiplimab Monotherapy for First Line Advanced NSCLC Patients with PD-L1 Expression ≥50%: 5-y Outcomes of EMPOWER-Lung 1

OA11.06 Cemiplimab Monotherapy for First Line Advanced NSCLC Patients with PD-L1 Expression ≥50%: 5-y Outcomes of EMPOWER-Lung 1

P3.12E.04 Long-Term Outcomes with Sotorasib in KRAS G12c-Mutated Advanced NSCLC from the Global Expanded Access Program (EAP) Study-436

P3.12E.04 Long-Term Outcomes with Sotorasib in KRAS G12c-Mutated Advanced NSCLC from the Global Expanded Access Program (EAP) Study-436

MA12.04 FLAURA2: Impact of Tumor Burden on Outcomes of 1L Osimertinib ± Chemotherapy in Patients with EGFR-mutated Advanced NSCLC

MA12.04 FLAURA2: Impact of Tumor Burden on Outcomes of 1L Osimertinib ± Chemotherapy in Patients with EGFR-mutated Advanced NSCLC

P4.11D.05 EGFR Neoantigen Peptide Vaccine Combined with Tislelizumab and Chemotherapy for Advanced NSCLC Resistant to EGFR-TKI Therapy

P4.11D.05 EGFR Neoantigen Peptide Vaccine Combined with Tislelizumab and Chemotherapy for Advanced NSCLC Resistant to EGFR-TKI Therapy

Pemetrexed and platinum with or without pembrolizumab for advanced non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis.

This meta-analysis aimed to evaluate the efficacy and safety of combining pemetrexed and platinum with or without pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC). A systematic search of PubMed, Embase, Cochrane Library, and Web Of Science databases was conducted to identify studies comparing pemetrexed and platinum with or without pembrolizumab in advanced NSCLC. Raw data were extracted from eligible studies to calculate Hazard Ratios (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), as well as rates of adverse events of all grades and those of Grade 3 or higher. Eight studies with 1639 patients occurred advanced NSCLC included. The group receiving pembrolizumab in combination with pemetrexed and platinum showed significant benefits in terms of OS (HR 0.63; 95% CI 0.54-0.73; p < 0.00001) and PFS (HR:0.64; 95% CI 0.48-0.85; p = 0.002) compared to the group receiving pemetrexed and platinum alone. However, this benefit was accompanied by a higher incidence of Grade 3 or higher adverse events (OR: 1.55; 95% CI 1.24-1.95; p = 0.0001). The combination of pemetrexed and platinum with pembrolizumab is recommended as a first-line treatment option for advanced NSCLC due to its significant efficacy benefits. However, the increased risk of Grade 3 or higher adverse events suggests the need for careful consideration and assessment when considering this regimen for second-line or subsequent therapy.

Long-term control by immune checkpoint inhibitors in a lung cancer patient with chronic kidney disease.

Immune checkpoint inhibitor (ICI) therapy has brought about a revolutionary advance in the treatment of advanced non-small cell lung cancer (NSCLC). Not a few patients with NSCLC have comorbid diseases. In patients who already have impaired renal function, particular attention must be paid to renal toxicity, a rare immune-related adverse events. Although there have been some case reports of ICI therapy for patients with advanced NSCLC undergoing hemodialysis, information on ICI therapy in patients with chronic kidney disease (CKD) is limited. We show herein a case with a successfully treated 75-year-old male patient with CKD and advanced NSCLC. His estimated glomerular filtration rate at the start of anticancer treatment was 40 mL/min/1.73 m2. Nivolumab and ipilimumab were administered, considering both the expectation of therapeutic efficacy and the avoidance of side effects. Ipilimumab was discontinued 1 year after the start of the treatment, and nivolumab was also terminated 2 years after the initiation of the treatment due to thyroid dysfunction as immune-related adverse event. Without worsening of CKD, the patient was able to control NSCLC with two immune checkpoint inhibitors for ≥ 3 years. Nivolumab and ipilimumab regimen might become one of the options for NSCLC patients with CKD. This report could provide some suggestions for the treatment of future patients who might experience a similar course of the therapy.

Association between epidermal growth factor receptor-tyrosine kinase inhibitors and venous thromboembolism among older patients with advanced non-small cell lung cancer.

Venous thromboembolism (VTE) risk is higher among patients with non-small cell lung cancer (NSCLC) and specific subgroups, including the elderly, but little is known about the VTE risk of different generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and whether the risk differs by demographic characteristics. This study aims to compare the risk of VTE (deep venous thromboembolism [DVT]; pulmonary embolism [PE]) between a third-generation EGFR-TKI and first/second-generation EGFR-TKIs and stratify VTE risk by sex, age, and race/ethnicity in third-generation EGFR-TKI users. Via the 2006-2019 Surveillance, Epidemiology, and End Results-Medicare database, this retrospective cohort study included older patients (aged ≥65 years) with advanced NSCLC who initiated on a third-generation EGFR-TKI (n=493) and first/second-generation EGFR-TKIs (n=1036). We estimated the hazard ratio (HR) and its 95% confidence interval (95% CI) with the Cox proportional hazards model. A third-generation EGFR-TKI had a significantly higher VTE risk than first/second-generation EGFR-TKIs (HR, 1.26 [95% CI, 1.01-1.57]; p=.037), with an elevated risk in males (HR, 2.16 [95% CI, 1.47-3.19]; p<.001), patients aged ≥75 years (HR, 1.38 [95% CI, 1.04-1.83]; p=.026), and non-Hispanic Whites (HR, 1.46 [95% CI, 1.10-1.95]; p=.010). Males consistently showed a significantly higher risk of DVT (HR, 2.49 [95% CI, 1.29-4.80]; p=.007) and PE (HR, 2.00 [95% CI, 1.29-3.11]; p=.002). A significantly higher risk of DVT (HR, 1.54 [95% CI, 1.00-2.37]; p=.050) and PE (HR, 1.47 [95% CI, 1.06-2.05]; p=.021) was shown in patients aged ≥75 years and non-Hispanic Whites, respectively. Among third-generation EGFR-TKI users, non-Hispanic Whites had a significantly higher risk of VTE (HR, 2.04 [95% CI, 1.03-4.02]; p=.041) and PE (HR, 2.88 [95% CI, 1.24-6.70]; p=.014) than non-Hispanic Asian/Pacific Islanders. Close monitoring of VTE events in high-risk patients is essential to promote early diagnosis and treatment.

Retrospective analysis of survival and safety of bevacizumab biosimilar and original drug combination chemotherapy in non-small cell lung cancer.

The advent of bevacizumab has considerably transformed the therapeutic landscape for non-small cell lung cancer (NSCLC) patients devoid of specific genetic mutations. A pivotal milestone has been reached with the recent approval of a bevacizumab biosimilar, following rigorous phase III clinical investigations, poised to augment NSCLC therapeutic strategies. This retrospective analysis encompasses a large-scale study conducted between January 2021 and December 2023, involving 1058 NSCLC patients (metastatic or locally advanced stages). The research design entailed a comparative assessment of the safety and efficacy profiles of combined therapies using the original bevacizumab and its biosimilar, adhering to RECIST v1.1 criteria. Adverse event grading was standardized using the National Cancer Institute's CTCAE v5.0. Notably, the biosimilar demonstrated an objective response rate (ORR) of 29.79% in 606 patients, closely paralleling the 27.41% ORR observed in 452 patients receiving the original drug, with insignificant risk differences (-0.03) and a risk ratio of 0.987, affirming equivalence. Progression-free survival (PFS) was influenced by radiation status, treatment lines, and regimen combinations, while dosage intensity and genetic factors had negligible impacts. The incidence of treatment-emergent adverse events (TEAEs) was slightly higher in the biosimilar group (75.11%) versus the original drug group (72.78%), with grade 3 or more severe TEAEs occurring in 23.6% and 18.5% of patients, respectively (Detailed criteria for the definition and assessment of TEAEs have been added to the Methods section, including the use of the National Cancer Institute's CTCAE v5.0 for grading). The study affirms that bevacizumab biosimilars offer equivalent therapeutic efficacy and a similar safety profile to the originator product in the management of locally advanced or metastatic NSCLC. The tolerability of the toxicity profile, coupled with the absence of unforeseen adverse reactions, underscores the viability of biosimilar bevacizumab as a valuable addition to NSCLC treatment regimens. These findings also imply potential benefits for a broader patient population beyond clinical trial confines through the adoption of biosimilar beta-adrenergic blocking agents.

Obesity and survival in advanced non-small cell lung cancer patients treated with chemotherapy, immunotherapy, or chemoimmunotherapy: a multicenter cohort study

BackgroundThe association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study.MethodsWe retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan–Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios.ResultsIn the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76–0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82–1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64–0.84), but no association observed in women (HR = 0.96, 95% CI 0.81–1.13, Pinteraction = 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores.ConclusionsObesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.

Efficacy and safety of anlotinib combined with S‑1 as a third‑ or later‑line treatment for advanced non‑small cell lung cancer in China: A systematic review and meta‑analysis.

Anlotinib is presently used as a third-line treatment for non-small cell lung cancer. However, it is not yet reported whether combining anlotinib with S-1 as a third- or later-line treatment offers superior outcomes compared with anlotinib alone. The present meta-analysis aimed to address this question by systematically searching the PubMed, Embase, Web of Science, Cochrane Library, CMB and China National Knowledge Infrastructure databases for eligible studies published from the establishment of the database to January 10, 2024. Primary outcomes of interest included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse effects, which were presented as hazard ratios and 95% CIs. The present analysis included 5 retrospective studies with a total of 317 patients and compared the outcomes of patients treated with a combination of anlotinib and S-1 (experimental group) compared with anlotinib alone (control group). The combination treatment significantly improved PFS, OS, ORR and DCR in the experimental group compared with the control group. Bone marrow suppression and fatigue were significantly higher in the experimental group compared with the control group. However, incidences of hypertension, proteinuria, gastrointestinal adverse reactions, hepatic and renal insufficiency and functional hand-foot syndrome were higher in the control group compared with the experimental group, but there was no statistical significance. In summary, combining anlotinib with S-1 may be more effective compared with anlotinib alone for treating advanced non-small cell lung cancer. Despite the higher incidence of adverse reactions with the combination therapy, these reactions could be considered manageable and controllable.

The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-smallcell lung cancer: A multicenter retrospective observational study.

For patients with advanced non-small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti-PD-1/PD-L1 antibodies. We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab-based regimens in later therapy lines. A total of 41 advanced NSCLC patients refractory to anti-PD-1/PD-L1 therapy were enrolled. More than half of the patients received cadonilimab-based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression-free survival for all evaluated patients was 108.0 days. Due to the short follow-up period, the median overall survival has not yet been reached. Treatment-related adverse events (TRAEs) and immune-related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma-glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab-based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti-PD-1/PD-L1 therapy.

Efficacy and Safety of MUC1 Antigen-Specific Vaccine as a Breakthrough Solution in the Treatment of Advanced Non-Small Cell Lung Cancer

Introduction: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of death for cancer patients globally. Most of the patients are diagnosed in advanced stage that can only receive conventional chemotherapy with low overall survival and low progression-free survival outcomes. With the advancement of technology, researchers have discovered that antigen-specific vaccine could be utilized to fight tumor cells. MUC1 antigen-specific vaccine is a novel solution that has been proved to be specific and accurate against NSCLC. In this study, we would like to present current best evidences regarding the efficacy and safety of MUC1 antigen specific vaccine in battling NSCLC. Methods: Literature search was conducted on databases, namely PubMed, Scopus, Cochrane, Science Direct, EBSCOhost, and Google Scholar up to August 27th 2022. Our inclusion criteria include randomized controlled trials in patients with advanced stage NSCLC, given MUC1 antigen-specific vaccine as treatment, compared to placebo as control group, and measured the efficacy in terms of overall survival and progression-free survival, quality of life, and adverse events. Results and discussion: Six randomized controlled trials were included in this review. Overall, longer overall survival and progression-free survival is observed in all studies. However, significance differed from study to study. This could be attributed to different patient characteristics and chemotherapy regimens used. MUC1 antigen-specific vaccine is more effective in patients who received concurrent chemoradiotherapy, high sMUC1 and ANA level, and non-squamous tumor type. Minimum adverse events were reported and incidence is similar with the control group. No negative impact on quality of life was observed. Conclusion: MUC1 vaccine showed a promising impact on improving patients’ overall survival and progression-free survival while ensuring patient’s safety. However, further studies with larger sample size are recommended on more specific populations, for instance, patients with concurrent chemotherapy.

Draw on advantages and avoid disadvantages: CT-derived individualized radiomic signature for predicting chemo-radiotherapy sensitivity in unresectable advanced non-small cell lung cancer

BackgroundPresently, the options of concurrent chemo-radiotherapy (CCR) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) are controversial and there is no reliable prediction tool to stratify poor- and good-responders. Although radiomic analysis has provided new opportunities for personalized medicine in oncological practice, the repeatability and reproducibility of radiomic features are critical challenges that hinder their widespread clinical adoption. This study aimed to develop a qualitative radiomic signature based on the within-sample rank of radiomics features, and to use this novel method to predict CCR sensitivity in LA-NSCLC, avoiding the variability of quantitative signatures to multicenter effect.MethodsWe retrospectively analyzed 125 patients with stage III NSCLC who received treatment from our hospital. Radiomic features were extracted from pretreatment plain CT scans and constructed as feature pairs based on their within-sample rank. Fisher and univariate Cox analyses were performed to select feature pairs significantly associated with patients’ overall survival (OS). NSCLC-Radiomic (R422) cohort including 104 NSCLC patients was used as an independent testing cohort. NSCLC-Radiogenomic (RG211) cohort with matched RNA sequencing profiles, was used for functional enrichment analysis to reveal the underlying biological mechanism reflected by the signature.ResultsA qualitative signature, consisting of 15 radiomic feature pairs (termed as 15-RiFPS), was developed based on the Genetic Algorithm, which could optimally distinguish responder from non-responder with significantly improved OS if they received CCR treatment (log-rank P = 0.0009, HR = 13.79, 95% CIs 1.83–104.1). The performance of 15-RiFPS was validated in an independent public cohort (log-rank P = 0.0037, HR = 2.40, 95% CIs 1.30–4.40). Furthermore, the transcriptomic analyses provided biological pathways (‘glutathione metabolic process’, ‘cellular oxidant detoxification’) underlying the signature.ConclusionsWe developed a CT-derived 15-RiFPS, which could potentially help predict individualized therapeutic benefit of CCR in patients with LA-NSCLC. Additionally, we investigated the underlying intra-tumoral biological characteristics behind 15-RiFPS which would accelerate its clinical application. This approach could be applied to a wider range of treatments and cancer types.

Detection of genomic alterations in liquid biopsies from patients with non-small cell lung cancer using FoundationOne Liquid CDx: a cost-effectiveness analysis

Objective Liquid biopsy (LB) is a non-invasive technique to detect genetic alterations by next-generation sequencing (NGS) when tissue biopsy is not available. This study aims to estimate in the Spanish setting, the cost-effectiveness of using FoundationOne Liquid CDx (F1L CDx), a novel blood-derived LB test based on NGS, versus non-molecular diagnosis (non-mDx) in patients with advanced non-small cell lung cancer (NSCLC) in whom tissue sampling is not feasible. Methods A joint model was developed combining a decision-tree with partitioned survival models to calculate the costs and health outcomes over a lifetime horizon, comparing F1L CDx in LB versus non-mDx. Only direct costs (expressed in €of 2023) were included and a 3% discount rate for future costs and effects was considered. Health outcomes were expressed in Life Years (LYs) and Quality-Adjusted Life Years (QALYs). Utilities and treatment efficacy were obtained from the literature. An expert panel of 11 Spanish oncologists determined the treatment allocation and validated all model inputs and assumptions. Several sensitivity analyses were performed to assess the robustness of the results. Results In a hypothetical cohort of 1,000 patients, LB using F1L CDx would detect 386 alterations, so those patients could be treated with targeted therapies or enrolled in clinical trials. Cost-effectiveness results showed that F1L CDx provides greater effectiveness than non-mDx (+383.95 LYs and +305.94 QALYs), with an additional cost of €2,898,308. The incremental cost-utility ratio was €9,473/QALY gained. The probabilistic sensitivity analysis confirmed the robustness of the cost-effectiveness results. Limitations Various limitations inherent to cost-effectiveness analyses were described. Conclusion LB with F1L CDx test is a cost-effective strategy in Spain for patients with advanced NSCLC without tissue sample available for molecular diagnosis, improving the personalized treatment of these patients.

Benmelstobart plus anlotinib in patients with EGFR-positive advanced NSCLC after failure of EGFR TKIs therapy: a phase I/II study

The effect of immune‐based therapies on patients with epidermal growth factor receptor (EGFR)-positive advanced non-small cell lung cancer (NSCLC) resistant to EGFR tyrosine kinase inhibitor (TKI) therapy remains unclear. The ALTER-L038 study aimed to evaluate efficacy and safety of a chemotherapy-free combination of benmelstobart, an anti-programmed cell death ligand 1 antibody, and anlotinib, a small-molecule multi-target anti-angiogenic TKI, in EGFR-positive advanced NSCLC patients who progressed after EGFR TKI therapy. Patients were enrolled in a phase I/II study. In phase I (dose-escalation), patients received anlotinib (8, 10, 12 mg) plus benmelstobart (1200 mg). Recommended phase II dose, determined during phase I, was used in phase II dose-expansion cohort. Primary endpoints were maximum tolerable dose in phase I and progression-free survival (PFS) in phase II. At the data cutoff date (March 10, 2024), 55 patients were enrolled in phase II dose-expansion cohort. Median PFS of patients included in phase II cohort was 9.0 months, median overall survival was 28.9 months, objective response rate was 25.5%, disease control rate was 87.3%, and median duration of response was 19.8 months. Incidence of grade ≥3 treatment-related adverse events in study population was 25.5% (14/55), whereas grade ≥3 immune-related adverse events occurred in 10.9% (6/55) of patients. Benmelstobart plus anlotinib showed promising anti-tumor efficacy with tolerable safety profile, supporting the value of further development of this convenient chemotherapy-free regimen for patients with EGFR-positive advanced NSCLC who progressed after EGFR TKI therapy. Trial Registration: ChiCTR1900026273.

Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study.

Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Eligible patients were aged ≥ 20years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9months; estimated survival rates at 12, 24, and 36months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240mg/day was consistent with previous findings. Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. ClinicalTrials.gov identifier NCT03046992.