MA03.05 BRAF Mutations Are Associated with Increased Benefit from PD1/PDL1 Blockade Compared with Other Oncogenic Drivers in Non-Small Cell Lung Cancer

Negrão, Marcelo V.; Skoulidis, Ferdinandos; Montesion, Meagan; Schulze, Katja; Bara, Ilze; Shen, V.; Hu, Shiping; Elamin, Yasir Y.; Le, Xiuning; Goldberg, Marcel; Wu, Chang-Jiun; Zhang, J.; Barreto, David S; Rinsurongkawong, Waree; Simon, George R.; Roth, Jack A.; Swisher, Stephen G.; Lee, Jaewon J.; Tsao, Anne S.; Papadimitrakopoulou, Vassiliki A.; Gibbons, Don L.; Glisson, Bonnie S.; Miller, VA; Alexander, Barbara; Frampton, G.; Albacker, Lee A.; Shames, D.; Heymach, John V.

doi:10.1016/j.jtho.2019.08.514

Cited by 6 publications

(7 citation statements)

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“…Differences in the distribution of PD-L1 between the BRAF V600E and non-V600E groups were observed, BRAF V600E expressed more PD-L1 (24). In contrast, Negrao et al showed that the rate of PD-L1 positivity (TPS ≥1%) in the V600E genotype (75.4%) was higher than that in non-V600E genotypes (55.8%) (25). Regarding the results of immunotherapy, the median PFS and OS of the non-V600E BRAF population were 5.4 months and 14.9 months, respectively (25).…”

Section: Discussionmentioning

confidence: 94%

Outcomes of non-small cell lung cancer patients with non-V600E BRAF mutations: a series of case reports and literature review

Lazar,

Fischbach,

Schott

et al. 2024

Front. Oncol.

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Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of cases of lung cancer. The standard first-line therapy for patients without oncogenic driver metastatic NSCLC is anti PD-L1 immune checkpoint inhibition (ICI) with platinum-based chemotherapy. Approximately 4% of NSCLC patients harbor BRAF mutations; the V600E mutation is the most common. Non-V600 mutations is an heterogeneous population and account for approximately 50% of BRAF-mutated NSCLC. BRAF mutations are classified into 3 functional classes based on their kinase activity and their signaling mechanism. The European Medicines Agency and the United States Food and Drug Administration have approved dabrafenib, an anti-BRAF tyrosine kinase inhibitor (TKI), in combination with trametinib, an anti-MEK TKI, for the treatment of patients with BRAF V600E-mutated metastatic NSCLC. The use of targeted therapies in NSCLC with BRAF non-V600E mutations remains controversial. There is a lack of guidelines regarding therapeutic options in non-V600E BRAF-mutated NSCLC. Herein, we presented 3 cases of NSCLC with BRAF non-V600E mutations and reviewed the current state of therapies for this particular population of lung cancer.

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Section: Discussionmentioning

confidence: 94%

Outcomes of non-small cell lung cancer patients with non-V600E BRAF mutations: a series of case reports and literature review

Lazar,

Fischbach,

Schott

et al. 2024

Front. Oncol.

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“…First, the races of the patients included in our study (all populations were Chinese) and the B-FIRST trial (most populations were White) were different, which may have biased the selection of the bTMB cutoff threshold. Second, patients with EGFR mutations and ALK fusions, which have been shown to be associated with low TMB and low PD-L1 expression, were not excluded from this study (21).…”

Section: Discussionmentioning

confidence: 99%

Unique profile on the progress free survival and overall survival in patients with advanced non-small cell lung cancer in the Qujing area, Southwest China

Ma¹,

Shi²,

Liu³

et al. 2023

Front. Immunol.

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BackgroundChina’s southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing.MethodsTissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy.ResultsIn cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations.ConclusionsThese findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.

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“…NSCLC with epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase rearrangements, or ROS1 mutations is currently recognized as a negative predictor of immunotherapy efficacy (40,41). NSCLC patients harboring EGFR mutations benefit less from ICI treatment despite high PD-L1 expression (42). Several studies have shown that PD-L1 expression is regulated by complex mechanisms, including EGFR.…”

Section: Specific Gene Alterationsmentioning

confidence: 99%

Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer

Wang

Feng

et al. 2023

Front. Oncol.

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The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors.

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MA03.05 BRAF Mutations Are Associated with Increased Benefit from PD1/PDL1 Blockade Compared with Other Oncogenic Drivers in Non-Small Cell Lung Cancer

Abstract: Conclusion: Taken together, the genetic variant of the ERAP1 rs469783 and NCF2 rs10911362 from the MHCI pathway genes may be a promising predictor of survival in NSCLC patients via ERAP1 and NCF2 expression alteration.

Cited by 6 publications

References 0 publications

Outcomes of non-small cell lung cancer patients with non-V600E BRAF mutations: a series of case reports and literature review

Outcomes of non-small cell lung cancer patients with non-V600E BRAF mutations: a series of case reports and literature review

Unique profile on the progress free survival and overall survival in patients with advanced non-small cell lung cancer in the Qujing area, Southwest China

Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer

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