Promising Results for a Subset of Lung Cancer Patients
- A potential treatment option that has shown some positive results for KRAS gene mutated non-small cell lung cancer patients is called sotorasib (brand name Lumakras).
- KRAS is a gene that makes a protein involved in cell growth, cell mutation, and cell death.
- A patient must get genetic testing done to indicate if they can qualify for this treatment option.
- Progression-free survival (PFS) was 25% for patients using Lumakras versus 10% for those using the chemotherapy drug docetaxel.
- It is important to note this study did not include a clear benefit in overall survival, a key standard to measure the efficacy of cancer treatment.
- Lumakras only targets the KRAS G12C mutation and not other KRAS mutations.
The research at the end of a randomized phase III trial found that the use of Lumakras in patients with KRAS G12C mutated NSCLC significantly improved progression-free survival (PFS). The KRAS mutation is an error in a protein in normal cells. Patients using Lumakras in oral pill form had a one-year PFS of 24.8%, versus a PFS of 10.1% for patients who received regular IV chemotherapy (docetaxel).
Read MoreWhile there are limitations to this study, the drug has been approved for treatment, as determined by a Food & Drug Administration-approved test, for patients who have received at least one systemic therapy, according to the federal agency.
What Is KRAS?
Prior to even asking your medical provider about this treatment, you must get genetic testing done to see if you have the KRAS subtype G12C mutation, the most common KRAS mutation in NSCLC.
"RAS" is a protein in cells that triggers a series of chemical reactions that tell cells when to divide and when to die. If a RAS gene is mutated, the protein is abnormal, causing the cell to be continuously "on," growing and dividing in an uncontrolled way.
Lung cancer remains the leading cause of cancer death in the United States. Non-small cell lung cancer makes up to about 80 – 85% of lung cancers, according to The American Cancer Society. The KRAS G12C gene mutation occurs in about 13% of NSCLCs. Several major advancements, such as immunotherapy and targeted therapies, have been released over the past years. However, despite these recent advancements, little has been available to help patients who have lung cancer with a KRAS mutation.
However, it's important to note that sotorasib only targets the KRAS G12C mutation and not other KRAS mutations.
Sotorasib Side Effects
Just like any medications you take, this drug can cause side effects. Everyone responds differently, and it's hard to know in advance how your body will react. The most common side effects seen in patients are:
- Diarrhea
- Muscle aches and pains
- Nausea
- Fatigue
- Liver dysfunction
- Cough
Perhaps the biggest red flag is liver toxicity. It was disclosed that six patients quit treatment because of this, and another two discontinued owing to drug-induced liver injury.
Dr. Patel says there were higher rates of transaminitis, which is when you have an elevated liver enzyme, and diarrhea in the sotorasib arm “raising the question if it was related to the timing of the last immunotherapy.”
“The financial toxicity of the drug is also something to consider when there is no OS (overall survival) benefit. Overall, sotorasib is another option in the 2nd line setting for KRAS G12C mutated NSCLC,” said Dr. Patel. “With a lack of OS (overall survival) benefit and financial toxicity, it will be important to see how sotorasib’s story unfolds further.”
The Study
The primary goal of the CodeBreak 200 study was to look at PFS (progression-free survival). This refers to the time between controlling cancer by inhibiting its growth and signs it started growing again. Progression-free survival doesn’t necessarily mean living longer, but more time when cancer does not get any worse.
- 345 patients with KRAS G12C-mutated NSCLC were included in the study.
- All patients had their disease progress after prior chemotherapy (platinum-based) and immunotherapy.
- Progression-free survival was evaluated after 12 months.
- On whether Lumakras improved how long patients could live, there wasn't a significant difference between the two treatment arms. That means the study was not able to demonstrate that overall survival (OS) was better with sotorasib. OS refers to the length of time that someone lives after starting a specific treatment.
Phase III Clinical Trial
A phase III trial compares new treatments with the best currently available treatment (the standard treatment). It aims to find out:
- Which treatment works better for a particular type of cancer
- More about the side effects
- How the treatment affects people's quality of life
“This treatment is definitely a viable treatment option for patients with tumors expressing this abnormal gene, found in about 10% of lung cancers,” Dr. David Carbone, director of the thoracic cancer center at The Ohio State University Exner Medical Center told SurvivorNet. “It is currently given after tumors become resistant to standard treatments with chemotherapy and immunotherapy.”
“There are typically limited options in this situation, but this drug adds a really good additional option for these patients,” adds Dr. Carbone.
What Are The Clinical Trial Phases?
There are four different phases in an interventional cancer clinical trial, each having a specific goal to establish. These phases can be summarized through the following points:
- Phase I: The first phase of the trial is initiated after a drug is approved and aims to find a safe dose for and determine the optimal method for drug administration. This phase involves a small number of volunteers (15-30 participants).
- Phase II: The second phase of the trial is initiated after a safe dose of the drug has been determined from the first phase, and it aims to test the effectiveness of the treatment. This phase involves around 100 volunteers or less.
- Phase III: In stages I and II, a drug has shown promising results. Phase III is initiated on a much larger scale and aims to compare a new treatment with traditional treatments. This phase involves from one hundred to several thousand volunteers.
- Phase IV: This phase starts after the approval of the drug and lasts for several years to make sure that there are no long-term effects or adverse events for the drug that hasn't been shown in the previous phase. This phase is also known as the post-marketing phase.
However, these phases are not written in stone. Some researchers can design protocols that merge phase I with II or phase II with III; this depends on the study design and research question originally put in place by the principal investigator.
Questions to Ask Your Doctor
- Has my cancer been tested for the KRAS gene?
- If positive for the KRAS gene, how will this affect my cancer treatment?
- Is there a specific medication I can use to target the KRAS gene? What will my treatment cost?
- How will I feel during treatment?
- Will I have side effects that last after the treatment?
- Should I get a second opinion?
- What is my prognosis?
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