380MO A phase II trial of atezolizumab, bevacizumab, pemetrexed and carboplatin combination for metastatic EGFR-mutated NSCLC after TKI failure

Lam, Tai Chung; Tsang, K. T.; Choi, Horyun; Lee, V.H.F.; Lam, Ka-On; Chiang, Chi‐Lu; So, Tsz Him; Chan, Wendy; Nyaw, S.F.; Lim, Farah Louise; Lau, James Siu Ki; Chik, Jeannie; Kong, Siyuan; Lee, A.W.M.

doi:10.1016/j.annonc.2020.10.374

Cited by 5 publications

(3 citation statements)

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“…The current study showed that patients with prior osimertinib treatment had a shorter mPFS than those without osimertinib treatment. This finding was consistent with the post-hoc analysis results of a phase 2 trial, which showed that patients with acquired resistance to osimertinib had a shorter PFS with atezolizumab combination therapy than those without osimertinib exposure [22]. Furthermore, the current study showed that prior osimertinib treatment was a poor prognosis factor, likely because patients exposed to osimertinib represented a subgroup that had exhausted multiple lines of TKI therapy and/or potentially acquired resistance EGFR mutations, such as T790M.…”

Section: Discussionsupporting

confidence: 90%

“…Notably, a survival benefit was also observed in patients with EGFR mutations who had received prior treatment with EGFR-TKIs [37]. In 2020, Lam et al reported the results of a phase 2 trial in which atezolizumab/bevacizumab/pemetrexed/carboplati n provided a response rate of over 60% and an mPFS of 9.4 months in patients with TKI-resistant, EGFRmutant, metastatic lung cancer [22]. More clinical trials are necessary to clarify whether atezolizumab combination therapy may be effective in patients with acquired resistance to EGFR-TKIs.…”

Section: Discussionmentioning

confidence: 99%

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Clinical outcomes of Atezolizumab Therapy for Previously-Treated Advanced-Stage Non-Small Cell Lung Cancer: A Real-World Study in Taiwan

Wu¹,

Chiang²,

Wang³

et al. 2022

J. Cancer

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Immune checkpoint inhibitors (ICIs) are the standard treatment for non-small-cell lung cancer (NSCLC). We assessed the clinical prognostic factors in NSCLC patients receiving atezolizumab as a second-or later-line (2L+) treatment. Data were retrospectively collected for NSCLC patients treated with atezolizumab from July 2017 to June 2019 at six medical centers in Taiwan. Clinical characteristics, treatment course and responses of patients were recorded. A total of 128 NSCLC patients received 2L+ atezolizumab, and the outcomes included a response rate of 10.2%, median progression-free survival (mPFS) of 3.5 months, and median overall survival (mOS) of 10.7 months. Eleven patients who had received osimertinib treatment before atezolizumab had a shorter mPFS (2.3 versus 3.5 months; p = 0.002) and mOS (4.8 versus 11.2 months; p < 0.001) than those without prior osimertinib treatment. Even for the subgroup of patients with EGFR-mutant non-squamous NSCLC, prior osimertinib was still associated with shorter PFS (2.3 versus 4.1 months; p = 0.006) and OS (4.8 versus 11.7 months; p < 0.001). Multivariate analysis revealed that prior osimertinib treatment correlated with not only shorter PFS (hazard ratio [HR]: 2.94; 95% confidence interval [CI], 1.34-6.47; p = 0.007) but also shorter OS (HR, 3.55; 95% CI,; p = 0.002). Patients with prior ICIs treatment (HR, 3.18; p = 0.002) or poor performance status (HR, 2.70; p = 0.001) had shorter OS. In conclusion, osimertinib treatment before atezolizumab therapy was associated with a shorter PFS and a poor prognosis in NSCLC patients in real-world settings. Further studies with larger sample sizes are needed to validate these observations.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of Atezolizumab Therapy for Previously-Treated Advanced-Stage Non-Small Cell Lung Cancer: A Real-World Study in Taiwan

Wu¹,

Chiang²,

Wang³

et al. 2022

J. Cancer

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“…Lam et al. recently reported the results of the Phase II NCT03647956 trial that enrolled 40 patients with metastatic EGFR m NSCLC that had progressed on EGFR TKI (57.5% osimertinib) ( 57 ). Patients were treated with atezolizumab + bevacizumab + pemetrexed-carboplatin until progression.…”

Section: Clinical Trials Of Immune Checkpoint Therapy In Advanced Egfr Mutant Nsclcmentioning

confidence: 99%

Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

et al. 2021

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Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitor combinations are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and active avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.

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Comparison of Chemotherapy Plus Pembrolizumab vs. Chemotherapy Alone in EGFR-Mutant Non–small-Cell Lung Cancer Patients

Chen¹,

Xu²,

Zhao³

et al. 2023

Clinical Lung Cancer

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380MO A phase II trial of atezolizumab, bevacizumab, pemetrexed and carboplatin combination for metastatic EGFR-mutated NSCLC after TKI failure

Cited by 5 publications

References 0 publications

Clinical outcomes of Atezolizumab Therapy for Previously-Treated Advanced-Stage Non-Small Cell Lung Cancer: A Real-World Study in Taiwan

Clinical outcomes of Atezolizumab Therapy for Previously-Treated Advanced-Stage Non-Small Cell Lung Cancer: A Real-World Study in Taiwan

Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

Comparison of Chemotherapy Plus Pembrolizumab vs. Chemotherapy Alone in EGFR-Mutant Non–small-Cell Lung Cancer Patients

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