Dataset Information

Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation.

ABSTRACT:

Purpose

To evaluate the outcomes of immune checkpoint inhibitor (ICI)-based treatments versus classical chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients who develop epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and to explore the population that may benefit from ICI-based therapy.

Materials and methods

All patients who had previously received EGFR-TKI therapy at two cancer centers in China and developed resistance to targeted therapies were included. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of the study cohort.

Results

A total of 132 patients were included. The median follow-up time for this cohort was 21.7 months (IQR, 14.8-28.8 months), calculated from the date of EGFR-TKI resistance. The median PFS and OS were 4.9 months (IQR, 2.8-9.2) and 13.5 months (IQR, 6.6-26.5 months), respectively. Multivariate analysis showed that ICI-based therapy could significantly improve OS when compared to the classic chemotherapy (hazard ratio [HR], 0.55; 95% CI, 0.34-0.88; P = 0.01) after adjusting for variables such as gender, age, mutation status, and brain or liver metastasis status. The combined modality of ICI plus chemotherapy could offer a long-term OS benefit in most subgroups, such as young (<65 years) patients, and those without secondary T790M mutations or absence of liver and brain metastases, and the populations with good Eastern Cooperative Oncology Group (ECOG) scores.

Conclusion

For patients presenting with EGFR-TKI resistance, ICI-based therapy could offer a more favorable survival than classical chemotherapy. The combination of ICI with chemotherapy may be the optimal modality for those with good ECOG PS scores.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC9445807 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation.

Cheng Yajie Y Yang Bin B Ouyang Wen W Jie Chen C Zhang Wei W Chen Gang G Zhang Junhong J Yu Jing J Xie Conghua C

Frontiers in oncology 20220823

<h4>Purpose</h4>To evaluate the outcomes of immune checkpoint inhibitor (ICI)-based treatments versus classical chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients who develop epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and to explore the population that may benefit from ICI-based therapy.<h4>Materials and methods</h4>All patients who had previously received EGFR-TKI therapy at two cancer centers in China and developed resistance to target ...[more]

PMID: 36081560

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Project description:IntroductionPlatinum-based chemotherapy is still the standard of care for Epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) patients after developing EGFR-TKI resistance. However, no study focusing on the role of immuno checkpoint inhibitor (ICI) based treatments for EGFR mutated NSCLC patients who carried programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50% progressed after EGFR-TKI therapy. In this study, we retrospectively investigated the outcomes of ICI-based treatments for EGFR mutated NSCLC patients carried PD-L1 TPS≥50% after developing EGFR-TKI resistance and to explore the population that may benefited from ICI-based treatment.MethodsWe retrospectively collected data of advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation at Shanghai Chest Hospital between January 2018 and June 2021. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of this study.ResultsA total of 146 patients were included. Up to June 20th, 2022, median follow-up was 36.7 months (IQR, 12.5-44.2 months). Among the population, 66 patients (45.2%) received chemotherapy, the remaning (54.8%) received ICI-based treatment, including 56 patients(70.0%) received ICI combined with chemotherapy (IC) and 24 patients (30.0%) received ICI monotherapy (IM). In IC group,31 patients received ICI combined with chemotherapy,19 patients received ICI combined with antiangiogenic therapy and remaing received ICI combined with chemotherapy and antiangiogenic therapy. Survival analysis shown that patients who received ICI-based treatment had better progress-free survival (PFS) and overall survival (OS) compared with those treated with other therapy (median PFS, 10.0 vs. 4.0 months, P<0.001; median OS, 39.5 vs. 24.2 months, P<0.001). What's more, patients who treated with IC treatment had a superior survival time than those received IM treatment (median PFS, 10.3 vs. 7.0 months, P<0.001; median OS, 41.6 vs. 32.4 months, P<0.001). Subgroup analysis found that the PFS and OS benefit of IC was evident in all subgroups.ConclusionsFor advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation, ICI-based treatment could provide a more favorable survival than classical chemotherapy. What' s more, compared with ICI monotherapy, ICI combined with chemotherapy seems to be the preferred treatment.

Project description:Previous studies have suggested that a variety of tumor driver genetic alterations affected the treatment efficacy of chemotherapy and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the tumor genetic alteration landscape and the treatment outcome of first-line chemotherapy and EGFR-TKIs in advanced NSCLC. A total of 94 patients with advanced NSCLC were recruited. All patients received first-line chemotherapy and/or EGFR-TKIs (either first- or second-generation EGFR-TKI, or third-generation EGFR-TKI) alone or sequentially. Prior to chemotherapy and/or EGFR-TKI treatment, plasma, effusion and/or tumor tissues from the included patients were subjected to next-generation sequencing, targeting 59 genes. The results indicated that the positive genetic alteration status prior to first-line chemotherapy was associated with prolonged progression-free survival (PFS) time compared with the negative status [9.1 vs. 4.0 months; hazard ratio (HR)=6.68; 95% CI, 2.25-19.82; P=0.001). Furthermore, patients with EGFR activating mutation harboring concomitant alterations exhibited a shorter PFS (11.1 vs. 7.4 months; HR=2.14; 95% CI, 1.03-4.44; P=0.04) and overall survival (OS) time [not reached (NR) vs. 32.8 months; HR=4.30; 95% CI, 1.41-13.16; P=0.01] than those without concomitant alterations, with first- and second-generation EGFR-TKI treatment. Similarly, patients with T79M mutation harboring concomitant alterations exhibited a shorter PFS (15.6 vs. 3.6 months; HR=9.48; 95% CI, 2.29-39.28; P=0.002) and OS time (NR vs. 32.8 months; HR=4.85; 95% CI, 1.16-20.29; P=0.03) with osimertinib treatment. Taken together, the results demonstrated that positive genetic alteration status predicted greater efficacy of first-line chemotherapy, while concomitant genetic alterations were associated with poor treatment outcome for first- or second-generation EGFR-TKI and third-generation EGFR-TKI treatment.

Project description:PurposeWe aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)-mutated patients with or without concomitant alterations.Materials and methodsThis multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR-tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.ResultsThe overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.ConclusionEGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Project description:BackgroundThe efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice.Patients and methods417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed.ResultsHigher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236).ConclusionsThis study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.

Project description:ObjectiveThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.MethodsA systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.ResultsA total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50-0.64; P <0.00001) and 0.70 (95% CI = 0.54-0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10-1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.ConclusionsCompared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.

Dataset Information

Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation.

Purpose

Materials and methods

Results

Conclusion

Publications

Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation.

Similar Datasets

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