Genomic features of response to combination immunotherapy in patients with advanced non-small cell lung cancer
By M. Hellmann, T. Nathanson, H. Rizvi, B. Creelan, F. Sánchez-Vega, Arun Ahuja, A. Ni, Jacki B. Novik, L. Mangarin, Mohsen Abu-Akeel and 22 more. Cancer Cell, 2018
921 citations recorded by the source corpus.
Summary Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole exome sequencing to examine non-small cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis. The low response rate in TMB low NSCLCs demonstrates that combination immunotherapy does not overcome the negative predictive impact of low TMB. This study demonstrates the association between TMB and benefit to combination immunotherapy in NSCLC. TMB should be incorporated in future trials examining PD-(L)1 with CTLA-4 blockade in NSCLC.
Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/a16da91021099b80494b709c704d6a1f6f62aaf4
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In Oncology
Citations in the corpus
- Tumor Mutation Burden and Efficacy of Nivolumab Monotherapy and in Combination With Ipilimumab in Small Cell Lung Cancer (2018, neutral): “…nivolumab plus ipilimumab is greatest in patients with high-TMB SCLC d TMB has a potential role as a biomarker for immunotherapy across lung cancers Hellmann et al., 2018, Cancer Cell 33, 1–9 May 14, 2018 ª 2018 Elsevier Inc. https://doi.org/10.1016/j.ccell.2018.04.001 Authors Matthew D.…”
- The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker (2020, background): “…et al., 2016; Shitara et al., 2018; Siefker-Radtke et al., 2018) Unfortunately, ICIs can also cause a number of unique immunerelated toxicities (Patel and Kurzrock, 2015; Postow and Hellmann, 2018) as well as accelerated progression, termed hyperprogression, in a subset of treated individuals.”
- ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. (2019, background): “1%), but there is a very high percentage of PD-L1 positive cases (75% of cases, using as total the number of cases with TMB-high and/ or MSI and/or PD-L1 positive), although in NSCLC PD-L1 and TMB-high have been demonstrated to be independent [98].”
- Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic (2018, methodology): “7 months [62] Nivolumab/ipilimumab NSCLC CM 568 FM NGS 10 mut/Mb 44% versus 12% 7.”