Final efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC)

Socinski, Mark A.; Velcheti, Vamsidhar; Mekhail, Tarek; Chae, Y.K.; Leal, Ticiana; Dowell, J.E.; Tsai, Ming-Hung; Dakhil, Christopher; Stella, Philip J.; Shen, Vincent K.; Hu, Sylvia; Paul, Shekelle; Shames, David S.; Schleifman, Erica; Fabrizio, David; Nowicki, Michaeł; Yun, Cindy; Phan, See; Kim, E.S.

doi:10.1093/annonc/mdz394.081

Cited by 52 publications

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“…HR for PFS and OS improved between high and low bTMB groups with increasing bTMB thresholds, from HR 1.16 and 0.95 at a threshold of bTMB greater than or equal to 10 to HR 0.59 and 0.44, respectively, at a threshold of bTMB greater than or equal to 20. 41 Other prospective studies of bTMB as a predictive biomarker for ICI (including the basket Blood First Assay Screening Trial [BFAST] trial) are ongoing. 42…”

Section: Clinical Trial Data Suggesting Use Of Blood Tmb As a Biomarkmentioning

confidence: 99%

The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee

Sholl

Hirsch

Hwang

et al. 2020

Journal of Thoracic Oncology

213

154

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Section: Clinical Trial Data Suggesting Use Of Blood Tmb As a Biomarkmentioning

confidence: 99%

The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee

Sholl

Hirsch

Hwang

et al. 2020

Journal of Thoracic Oncology

213

154

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“…However, patients at this prespecified bTMB cutoff only had numerical benefit for PFS and OS. 12 Two possible reasons might explain this result. First, tumor mutational burden is dynamic and could be changed after treatments.…”

Section: Discussionmentioning

confidence: 96%

“…11 However, a prospective, phase II, B-F1RST study only showed a trend toward a PFS benefit (hazard ratio (HR) = 0.66; 90% confidence interval (CI): 0.42-1.02; P = .12) and an OS benefit (HR = 0.77; 90% CI: 0.41-1.43; P = .48). 12 Cancer is a genetic disease, and multiple genetic mutations may lead to resistance to therapy, including immunotherapy. 13 Recent studies revealed that bTMB reflected overall tumor burden.…”

Section: Introductionmentioning

confidence: 99%

A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab

Nie

Qian

et al. 2020

OncoImmunology

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A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both P non-linearity < 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy.

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“…Therefore, the optimal gene panel and bTMB threshold should be better adjusted for each situation. A first-line B-F1RST trial [21] tried to predict survival with atezolizumab by using bTMB cut-point 16, which was identified in the prior study based on subsequent-line patients [1], and they failed to obtain significant results for OS or PFS. Dynamic change of ctDNA load and bTMB from treatment-naïve patients to previously-treated patients might account for this inconsistency.…”

Section: How Could Btmb Threshold and Gene Panel Design For Particulamentioning

confidence: 99%

Viewpoint: The Current Advances and Future Optimization of Blood-based Tumor Mutation Burden as a Biomarker for Cancer Immunotherapy

A¹

2021

Preprint

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Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

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Final efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC)

Cited by 52 publications

References 0 publications

The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee

The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee

A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab

Viewpoint: The Current Advances and Future Optimization of Blood-based Tumor Mutation Burden as a Biomarker for Cancer Immunotherapy

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