Atezolizumab Treatment of Tumors with High Tumor Mutational Burden from MyPathway, a Multicenter, Open-Label, Phase IIa Multiple Basket Study

Friedman, Claire F.; Hainsworth, John D.; Kurzrock, Razelle; Spigel, David R.; Burris, Howard A.; Sweeney, Christopher J.; Meric‐Bernstam, Funda; Wang, Yong; Levy, Jonathan; Grindheim, Jessica; Shames, David S.; Schulze, Katja; Patel, Arisha; Swanton, Charles

doi:10.1158/2159-8290.cd-21-0450

Cited by 60 publications

(40 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This discovery led to several tissue-agnostic regulatory approvals, granted on the basis of the overall response and duration of response activity observed in single-group studies. 1,2 Approvals to date include anti-PD-1 antibodies for tumours harbouring mismatch repair deficiency or microsatellite instability 1,3,4 or a high tumour mutational burden (≥10 mut/Mb), 5 as well as TRK inhibitors for NTRK fusion-positive tumours. 2,6 A common pattern associated with tissue-agnostic approvals is that the enrolling biomarker is present with a higher frequency in certain so-called anchor tumour types (the tumour types in which the qualifying alteration is most common), and much less commonly in a long tail of additional cancer types, a pattern also observed with RET fusions.…”

Section: Introductionmentioning

confidence: 99%

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial

Subbiah¹,

Wolf²,

Konda³

et al. 2022

The Lancet Oncology

227

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial

Subbiah¹,

Wolf²,

Konda³

et al. 2022

The Lancet Oncology

227

View full text Add to dashboard Cite

“…Another expert voted R because of the absence of the cut‐off for TMB‐high for each cancer type. Regarding tissue TMB, it has been suggested that the cut‐off for the efficacy of ICI depends on the drug used and cancer type 31 …”

Section: Results and Meeting Outcomesmentioning

confidence: 99%

Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors

et al. 2022

View full text Add to dashboard Cite

Comprehensive genomic profiling is increasingly used to facilitate precision oncology based on molecular stratification. In addition to conventional tissue comprehensive genomic profiling, comprehensive genomic profiling of circulating tumor DNA has become widely utilized in cancer care owing on its advantages, including less invasiveness, rapid turnaround time, and capturing heterogeneity. However, circulating tumor DNA comprehensive genomic profiling has some limitations, mainly false negatives due to low levels of plasma circulating tumor deoxyribonucleic acid and false positives caused by clonal hematopoiesis. Nevertheless, no guidelines and recommendations fully address these issues. Here, an expert panel committee involving representatives from 12 Designated Core Hospitals for Cancer Genomic Medicine in Japan was organized to develop expert consensus recommendations for the use of circulating tumor deoxyribonucleic acid‐based comprehensive genomic profiling. The aim was to generate guidelines for clinicians and allied healthcare professionals on the optimal use of the circulating tumor DNA assays in advanced solid tumors and to aid the design of future clinical trials that utilize and develop circulating tumor DNA assays to refine precision oncology. Fourteen clinical questions regarding circulating tumor deoxyribonucleic acid comprehensive genomic profiling including the timing of testing and considerations for interpreting results were established by searching and curating associated literatures, and corresponding recommendations were prepared based on the literature for each clinical question. Final consensus recommendations were developed by voting to determine the level of each recommendation by the Committee members.

show abstract

“…Based on this evidence, FDA-approved Pembrolizumab on June 16, 2020 for the treatment of refractory unresectable or metastatic solid tumors of TMB-H, defined by 10 mutations/megabase (muts/MB) based on the FoundationOne CDx assay. However, a latest multicenter, open-label, phase 2a multiple basket study in pan-cancers [ 119 ], which accounts for the majority of CRC, reported the value of TMB as a predictor of atezolizumab treatment. The results exhibited that the ORR of MSI-H and MSI-L in patients with TMB ≥ 16 mut/MB was 54.5% and 31.0%, respectively.…”

Section: Predictive Biomarkers Of Response In Icb Therapymentioning

confidence: 99%

Exploring immunotherapy in colorectal cancer

et al. 2022

View full text Add to dashboard Cite

Chemotherapy combined with or without targeted therapy is the fundamental treatment for metastatic colorectal cancer (mCRC). Due to the adverse effects of chemotherapeutic drugs and the biological characteristics of the tumor cells, it is difficult to make breakthroughs in traditional strategies. The immune checkpoint blockades (ICB) therapy has made significant progress in the treatment of advanced malignant tumors, and patients who benefit from this therapy may obtain a long-lasting response. Unfortunately, immunotherapy is only effective in a limited number of patients with microsatellite instability—high (MSI-H), and segment initial responders can subsequently develop acquired resistance. From September 4, 2014, the first anti-PD-1/PD-L1 drug Pembrolizumab was approved by the FDA for the second-line treatment of advanced malignant melanoma. Subsequently, it was approved for mCRC second-line treatment in 2017. Immunotherapy has rapidly developed in the past 7 years. The in-depth research of the ICB treatment indicated that the mechanism of colorectal cancer immune-resistance has become gradually clear, and new predictive biomarkers are constantly emerging. Clinical trials examining the effect of immune checkpoints are actively carried out, in order to produce long-lasting effects for mCRC patients. This review summarizes the treatment strategies for mCRC patients, discusses the mechanism and application of ICB in mCRC treatment, outlines the potential markers of the ICB efficacy, lists the key results of the clinical trials, and collects the recent basic research results, in order to provide a theoretical basis and practical direction for immunotherapy strategies.

show abstract

Atezolizumab Treatment of Tumors with High Tumor Mutational Burden from MyPathway, a Multicenter, Open-Label, Phase IIa Multiple Basket Study

Cited by 60 publications

References 37 publications

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial

Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors

Exploring immunotherapy in colorectal cancer

Contact Info

Product

Resources

About