Advanced Targeted Chemotherapy and Precision Medicine for Colon Cancer

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• Targeted Colon Cancer Medications
• Molecular Profiling for Treatment
• Microsatellite Instability and Immunotherapy
• Survival Rates in Metastatic Cancer
• New Approved Colon Cancer Drugs
• Future of Colon Cancer Research
• Full Transcript

Targeted Colon Cancer Medications

Dr. Heinz-Josef Lenz, MD, describes a new era in advanced colon cancer treatment powered by targeted chemotherapy. These medications, used with traditional chemotherapy backbones, dramatically increase tumor shrinkage efficacy. Key drug classes include antibodies that target the angiogenic pathway, such as Ramucirumab (Cyramza) and Bevacizumab (Avastin), and Epidermal Growth Factor Receptor (EGFR) inhibitors like Panitumumab (Vectibix) and Cetuximab (Erbitux).

This combined approach can achieve a 60% to 70% response rate, meaning at least a 50% volume reduction in metastatic tumors. Dr. Heinz-Josef Lenz, MD, emphasizes that this powerful tumor shrinkage opens the window for potentially curative surgical intervention in more patients.

Molecular Profiling for Treatment Selection

The choice of targeted treatment is a critical life-or-death decision guided by molecular profiling. Dr. Heinz-Josef Lenz, MD, explains that testing for specific genetic mutations like KRAS and NRAS is now standard. These tests determine if a patient's tumor will respond to EGFR inhibitor medications.

This personalized medicine approach allows oncologists to select the most effective chemotherapy protocol from the start. Dr. Heinz-Josef Lenz, MD, notes that this is just the beginning, as more molecular alterations are being identified that can predict treatment efficacy and help avoid unnecessary toxicity.

Microsatellite Instability and Immunotherapy

Another crucial molecular marker is Microsatellite Instability (MSI), which indicates a mutation in DNA mismatch repair genes. Dr. Heinz-Josef Lenz, MD, references a landmark publication in the New England Journal of Medicine showing that colon cancer patients with MSI-high tumors have an "unbelievable response" to new immunomodulatory treatments.

This discovery exemplifies how molecular subtyping is fracturing colon cancer from one disease into many. Identifying these subtypes allows doctors to match patients with highly effective, often less toxic, treatments like immunotherapy, which were not previously considered standard for colorectal cancer.

Improved Survival Rates in Metastatic Cancer

The impact of these advances is quantified by a dramatic improvement in survival statistics. Dr. Heinz-Josef Lenz, MD, states that the old paradigm—that a patient with metastatic colorectal cancer will die—is no longer true. Where survival was once only 8 months without effective treatment, the median survival for newly diagnosed patients is now over 30 months.

This represents a quadrupling of median survival over the past decade. Furthermore, Dr. Heinz-Josef Lenz, MD, highlights that these numbers do not even account for the subset of patients who are now completely cured of metastatic disease, a previously unthinkable outcome.

Newly Approved Colon Cancer Drugs

The treatment arsenal continues to expand with newly approved medications. Dr. Heinz-Josef Lenz, MD, discusses Regorafenib (Stivarga), approved in 2013, which improves both progression-free and overall survival. Another significant addition is TAS-102 (Lonsurf), whose clinical trial results were also published in the New England Journal of Medicine.

Dr. Heinz-Josef Lenz, MD, notes that a NEJM publication signifies a new standard of care. TAS-102 has been shown to improve survival outcomes, further enriching the options available to oncologists and patients fighting advanced colon cancer.

Future of Colon Cancer Research

Dr. Lenz describes an incredibly exciting future for colon cancer research focused on precision medicine. The goal is to continue dissecting the disease into its molecular subtypes to better predict which patients will benefit from specific treatments.

This approach promises therapies with higher efficacy and lower toxicity. The interview with Dr. Anton Titov, MD, concludes with Dr. Lenz's optimism that the field will not only develop new drugs but will cure an increasing number of patients with metastatic colon cancer.

Full Transcript

The full transcript of the discussion between Dr. Anton Titov, MD, and Dr. Heinz-Josef Lenz, MD, provides a comprehensive overview of the evolving landscape of targeted colon cancer therapy. It details the mechanisms of action for various drug classes and the critical importance of genetic testing to guide treatment decisions for improved patient outcomes.

Full Transcript

Dr. Heinz-Josef Lenz, MD: Ramucirumab (IMC 1121B, Cyramza) and bevacizumab (Avastin). Epidermal Growth Factor Receptor (EGFR) pathway inhibitors: panitumumab (Vectibix) and cetuximab (Erbitux). We had regorafenib (Stivarga) approved. A new colon cancer treatment medication, TAS-102 (Lonsurf), is now approved.

I think we are getting access to new effective treatments for colon cancer that we didn't have in the past.

We know that more effective targeted medications were developed to treat colorectal cancer. Their use with chemotherapy backbones increases the efficacy of tumor shrinkage incredibly. Such targeted colorectal cancer medications are antibodies that target the angiogenic pathway: ramucirumab (IMC 1121B, Cyramza) and bevacizumab (Avastin).

There are also medications that target the Epidermal Growth Factor Receptor (EGFR) pathway: panitumumab (Vectibix) and cetuximab (Erbitux). Over the last couple of years, we are reaching 60% to 70% response rate of colorectal cancer tumors. It means 50% volume reduction of metastatic colon cancer tumors with our chemotherapy.

Targeted chemotherapy opens even further the window for surgical treatment. The choice of chemotherapy in combination with new targeted medications is important for patients with newly diagnosed colon cancer.

The choice of treatment makes a difference between life and death. That is a very important concept to understand. We are only beginning to use molecular profiling of colorectal cancer tumors.

We already have introduced molecular tumor markers. They allow us to distinguish what antibodies would work most effectively in this colon cancer patient. Testing for KRAS and NRAS is now giving us the option to use EGF receptor inhibitors: panitumumab (Vectibix) or cetuximab (Erbitux).

We are already making very nice progress to select and personalize chemotherapy for colon cancer. We decide on chemotherapy protocol after studying the molecular profile of the colorectal cancer tumor. But this is only the beginning.

We already know we can identify additional molecular alterations in colon cancer tumors. Such molecular changes are not only important for diagnosis of colon cancer; molecular markers also predict the efficacy of new treatments.

We had a publication in the New England Journal of Medicine. We showed that colorectal cancer tumor has a Microsatellite Instability (MSI). These patients have an unbelievable response to new immunomodulatory treatments. Microsatellite Instability means a mutation in DNA mismatch repair genes.

I think the future of colon cancer treatment is extremely exciting. We understand and dissect out colon cancer from one type of disease into many different colon cancer types. We know which patients will benefit differentially from new treatments for colon cancer.

We will know which colon cancer treatment often has less toxicity and higher efficacy.

This is an incredibly exciting time to be involved in colon cancer research. Because the old paradigm was simple: patient with metastatic colorectal cancer will die. That paradigm is not true anymore.

The progress in colon cancer treatment is huge. It is reflected in the new colorectal cancer clinical trials. Patient with newly diagnosed colon cancer now has the median survival over 30 months.

Sometimes we look backwards for patients with colorectal cancer and no treatment. Their survival was 8 months. Over the last 10 years, we quadrupled the median survival of patients with metastatic colon cancer.

This is not even counting the patients who we cured completely from colorectal cancer.

I think it's a very new area of colon cancer research that opens up incredible opportunity in the future. We will not only develop new medications, but we will cure more patients with metastatic colon cancer.

This year we already have seen incredible new data on new colon cancer treatment medications. In 2013, we had a new medication, regorafenib (Stivarga), approved. Regorafenib improved progression-free survival and overall survival of patients with colorectal cancer.

We have another new colon cancer treatment medication approved. It is called TAS-102, trade name Lonsurf. The results of clinical trial for colon cancer treatment were published in the New England Journal of Medicine.

Dr. Anton Titov, MD: New England Journal of Medicine (NEJM) is the most well known medical journal in the world.

Dr. Heinz-Josef Lenz, MD: That's correct. NEJM publication is a really major accomplishment. Clinical trial results published in NEJM are usually the standard of care or the paradigm for disease treatment.

This medication is called TAS-102 (Lonsurf). It also improved progression-free survival and overall survival of patients with colon cancer. I think we are getting access to new effective treatments for colon cancer that we didn't have in the past.

These new colon cancer medications enrich our armamentarium of treatment options for patients with colorectal cancer.