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KRAS G12C-Mutant Non-Small Cell Lung Cancer: Biology, Developmental Therapeutics, and Molecular Testing - PubMed

Mutation in the gene that encodes Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogenic driver in advanced non-small cell lung cancer, occurring in approximately 30% of ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/33618059/

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Targeting KRAS in Solid Tumors: Current Challenges and Future Opportunities of Novel KRAS Inhibitors - PubMed

Activating mutations in RAS family proteins are found in ~25% of all human cancers. Different solid tumors are correlated with mutations in certain isoforms of RAS, with Kirsten RAS (KRAS) ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34064352/

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KRAS Secondary Mutations That Confer Acquired Resistance to KRAS G12C Inhibitors, Sotorasib and Adagrasib, and Overcoming Strategies: Insights From the In Vitro Experiments - PubMed

We identified many secondary KRAS mutations causing resistance to sotorasib, adagrasib, or both, in vitro. The differential activities of these two inhibitors depending on the secondary mutations suggest sequential use ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/33971321/

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Targeting KRAS in non-small cell lung cancer: recent progress and new approaches - PubMed

Rat sarcoma (RAS) is the most frequently mutated oncogene in human cancer, with Kirsten rat sarcoma (KRAS) being the most commonly mutated RAS isoform. Overall, KRAS accounts for 85% of ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34089836/

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researchers show that PET/CT images can be used to measure levels of the PD-L1 biomarker of non-small cell lung cancer (NSCLC) patients in a non-invasive manner and, in turn, predict ..... see more

Moffitt Researchers Develop Non-invasive Approach to Measure Biomarker Levels, Predict Outcomes in Lung Cancer Patients

TAMPA, Fla. - Tests that analyze biomarkers are used during cancer management to guide treatment and provide information about patient prognosis. These tests are often performed on tissue biopsy samples ..... see more

Source : https://moffitt.org/newsroom/press-release-archive/moffitt-researchers-develop-non-invasive-approach-to-measure-biomarker-levels-predict-outcomes-in-lung-cancer-patients/

Guardant 360 FDA Approval as First and Only Liquid Biopsy Companion Diagnostic for Amgen’s LUMAKRAS™ (sotorasib) KRASG12C Inhibitor for Use in Advanced Non-Small Cell Lung Cancer
®-CDx-Receives-FDA-Approval-as-First-and-Only-Liquid-Biopsy-Companion-Diagnostic-for-Amgen’s-LUMAKRAS™-sotorasib-KRASG12C-Inhibitor-for-Use-in-Advanced-Non-Small-Cell-Lung-Cancer
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Guardant360® CDx Receives FDA Approval as First and Only Liquid Biopsy Companion Diagnostic for Amgen's LUMAKRAS™ (sotorasib) KRASG12C Inhibitor for Use in Advanced Non-Small Cell Lung Cancer

REDWOOD CITY, Calif.--()--Guardant Health, Inc. (Nasdaq: GH) announces that the U.S. Food and Drug Administration (FDA) has approved the Guardant360 ® CDx test as the first and only liquid biopsy ..... see more

Source : https://www.businesswire.com/news/home/20210528005396/en/Guardant360

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  • from Pathologist Connect 6 days 21 hours
    The majority of liquid biopsy testing is done without involvement of pathology. I bet my experience is not unique. This is a loss for everyone, representing a missed opportunity for Show More
  • 1 week
    Please share your thoughts on Guardant 360. In which patients do you plan to use the test?
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Sotorasib for Lung Cancers with KRAS p.G12C Mutation - PubMed

In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C-mutated NSCLC. (Funded by Amgen and the ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34096690/

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  • 1 week
    Key Points • In the current Phase 2 trial published in NEJM, investigators assessed the activity of sotorasib (960 mg PO qd) in patients with KRAS p.G12C–mutated advanced NSCLC who were Show More
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Metabolic reprograming of antioxidant defense: a precision medicine perspective for radiotherapy of lung cancer? - PubMed

Radiotherapy plays a key role in the management of lung cancer patients in curative and palliative settings. Traditionally, radiotherapy was either given alone or in combination with surgery, classical cytotoxic ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34110407/

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Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue - PubMed

Epithelial tissues are highly sensitive to anisotropies in mechanical force, with cells altering fundamental behaviors, such as cell adhesion, migration, and cell division. 1-5 It is well known that, in ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34111402/

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KRAS-dependent cancer cells promote survival by producing exosomes enriched in Survivin - PubMed

Mutations in KRAS frequently occur in human cancer and are especially prevalent in pancreatic ductal adenocarcinoma (PDAC), where they have been shown to promote aggressive phenotypes. However, targeting this onco-protein ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34111513/

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Sotorasib is a selective irreversible inhibitor of the G12C-activated KRAS oncogene, present in approximately 13% of non–small-cell lung cancers. In a single-group, phase 2 trial involving 126 patients with previously ..... see more

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Diagnostic testing companies should do a better job of turning around biomarker test results for lung cancer patients, according to a survey reported at the American Society of Clinical Oncology ..... see more

Oncologists urge faster biomarker results for lung cancer patients

Out of 170 clinicians polled, the vast majority (98%) said that they felt it was important to get biomarker test results back in from one to two weeks, but while ..... see more

Source : https://www.labpulse.com/index.aspx?sec=sup&sub=gen&pag=dis&ItemID=802127

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Targeting KRAS in Solid Tumors: Current Challenges and Future Opportunities of Novel KRAS Inhibitors - PubMed

Activating mutations in RAS family proteins are found in ~25% of all human cancers. Different solid tumors are correlated with mutations in certain isoforms of RAS, with Kirsten RAS (KRAS) ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34064352/

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  • 1 week 6 days
    Key Points • In the current review, authors examined the role of the KRAS mutation in different solid tumors, as well as examining KRAS inhibitors that have come to the fore. • Show More
Michael Misialek from Pathologist Connect Commented on a Post
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40 years of research produces first KRAS-targeted therapy

After almost 40 years of research, the first KRAS-targeted therapy has been approved. The drug sotorasib (Lumakras) is an inhibitor of the RAS GTPase family.

Sotorasib was approved by the FDA on May 28, 2021. It is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), who have received at least one prior systemic therapy. Diagnosis is determined by an FDA-approved test in patients who had disease progression  after receiving an immunotherapy or chemotherapy. Available in 120 mg tablets, 960 mg of sotorasib is taken by mouth daily.

The approval of sotorasib was based on results from the CodeBreak 100 trial, in which 124 locally advanced or metastatic NSCLC patients with KRAS G12C mutations were administered sotorasib 960 mg orally daily until disease progression. In these patients, their cancer had previously progressed during or after chemotherapy, immunotherapy, or both.

One primary outcome in the study was the objective response rate (ORR), which was 36% (95% CI: 28%, 45%), with the other primary outcome being a median response duration of 10 months. Furthermore, 81% of patients attained disease control, which was defined as the number of patients who achieved complete response, partial response, and stable disease lasting 3 or more months.

Diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough were the most common adverse reactions, occurring in 20% or more of patients. Laboratory anomalies occurring in 25% or more of patients included lymphocytopenia, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium.

Share your thoughts about the efficacy of sotorasib and how this may affect how you test and treat NSCLC.

Sources:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214665s000lbl.pdf

https://www.amgen.com/newsroom/press-releases/2021/05/fda-approves-lumakras-sotorasib-the-first-and-only-targeted-treatment-for-patients-with-kras-g12cmutated-locally-advanced-or-metastatic-nonsmall-cell-lung-cancer

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-sotorasib-kras-g12c-mutated-nsclc

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  • from Pathologist Connect 1 week 6 days
    Dr. Ferdinandos Skoulidis, PI at MD Anderson states “Sotorasib only works in patient with KRAS G12C-mutated nonsmall cell lung cancer but it appears, based on this data, that there is Show More
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FDA Approves First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test

Today, the U.S. Food and Drug Administration approved the first liquid biopsy companion diagnostic that also uses next-generation sequencing (NGS) technology to identify patients with specific types of mutations of ..... see more

Source : https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test

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Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer - PubMed

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34073318/

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KRAS and EGFR Mutations Differentially Alter ABC Drug Transporter Expression in Cisplatin-Resistant Non-Small Cell Lung Cancer - PubMed

Lung carcinoma is still the most common malignancy worldwide. One of the major subtypes of non-small cell lung cancer (NSCLC) is adenocarcinoma (AC). As driver mutations and hence therapies differ ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/34065402/

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Coverage from Sunday, June 6th at the 2021 ASCO Virtual Conference

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Coverage from Saturday, June 5th at the 2021 ASCO Virtual Conference

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Coverage from Friday, June 4th at the 2021 ASCO Virtual Conference

Click on the icon above to preview and download our full comprehensive coverage from Day 1 at the The 2021 ASCO Conference