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
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Anonymous UserAugust 18, 2021KRAS was an undrugabble biomarker, and now with Sotorasib we have an oral oncolytic for G12C in second line and beyond, and highlights the importance of comprehensive genomic testing, and how to sequence these agents
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M MerrickAugust 17, 2021Great to now have targeted therapy for KRAS mutation in NSCLC. KRAS G12C is relatively common and currently testing patients to determine if they are candidates for sotorasib
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Ali MirmiranAugust 10, 2021I think the efficacy of Sotorasib is rather good. As a result, I am now routinely checking for KRAS in my NSCLC patients.
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Anonymous UserAugust 01, 2021I I've been waiting to have a drug that targets KRAS and finally here we are. I have already started using Sotorasib in one of my patient this week; I hope they have G12D drug and other subypes also. otherwise it is pretty impressive data with Code Break Trial
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Connie Batlevi, Assistant Attending, Inpatient Director of Lymphoma ServiceJuly 28, 2021Amazing work to get to the first KRAS inhibitor. The FDA approval for KRAS G12C mutation based on any FDA-approved test also equally interesting as it opens up cfDNA testing for patient selection. Kudos!
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Vijay RaoJuly 24, 2021KRAS is a very common mutation in NSCLC and the G12C is the most commo KRAS mutation. The codebreak trial showed a good response rate, duration of response and tolerance.
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Thomas Cartwright, Ocala Oncology/FCAJuly 24, 2021Order NGS on all NSCLC patients. KRAS G12C common in lung cancer and sotorasib is reasonably well tolerated and has good efficacy. Interesting to see combination data and if sotorasib effective in other cancers with KRAS mutations such as colon cancer.
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Sherif BadawyJuly 23, 2021Sotorasib has shown promising clinical benefits in NSCLC patients with reasonable efficacy data, testing all patients 100% is our goal
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Prabhsimranjot SinghJuly 22, 2021Very excited to have another targeted therapy In NSCLC, impressed with results of DCR and tolerance. I am just trying to figure out how to test previous patients.
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Daya Sharma, MEDSTAR WASHINGTON HOSPITAL CENTERJuly 22, 2021Incidence of KRAS G12c is 20% much higher than other mutations. This is very wel come new option of pts.I am planning to use asap
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Marc BraunsteinJuly 22, 2021Given the recently published data, we are now testing all patients for KRAS G12C mutations and would use sotorasib if the mutations were identified given KRAS role as a driver mutation.
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Anonymous UserJuly 22, 2021Sotorasib is a welcome inclusion in the treatment armamentarium for NSCLC. KRAS G12C is present in 13% of NSCLC, 2nd to presence of EGFR mutation in NSCLC. ORR of 40% is quite good. Tolerability is acceptable. I am looking forward to treating my first patient with this drug. It will interesting to see how we build on the success of Sotorasib i.e treatment that works after development of resistance to this drug etc.
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Michael Misialek, Associate Chair of PathologyJune 08, 2021Dr. 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 a signal that it might work better in KRAS G12C-mutated nonsmall cell lung cancer that harbor a co-mutation in STK11, particularly when KEAP1 … is wild type,”
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Michael Misialek, Associate Chair of PathologyJune 08, 2021Dr. 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 a signal that it might work better in KRAS G12C-mutated nonsmall cell lung cancer that harbor a co-mutation in STK11, particularly when KEAP1 … is wild type,”
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Michael Misialek, Associate Chair of PathologyJune 08, 2021Dr. 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 a signal that it might work better in KRAS G12C-mutated nonsmall cell lung cancer that harbor a co-mutation in STK11, particularly when KEAP1 … is wild type,”