Over the course of more than 35 years of medical practice, Carbone has experienced a massive change in the way cancer is treated. He emphasizes how the development of targeted therapies and biomarker testing to match patients with the right therapy has made the biggest difference in the outcome of cancer treatment. Despite their success in the clinic, there are still multiple barriers to the widespread implementation of this type of tests.
In recent years, there have been multiple approvals of targeted therapies for patients with early-stage forms of lung cancer, such as EGFR- and ALK-targeted therapies, as well as immunotherapies targeting PD-L1 biomarkers.
In this Q&A with BioPharma-Reporter, Carbone discusses how these medical advancements have changed the way we treat cancer and what the healthcare industry needs to do to make the most of these life-changing innovations.
How has biomarker testing evolved over the years and what is its current role in personalized cancer care?
Biomarker testing basically wasn't done decades ago when I started in lung cancer therapy. But it's evolved from one or two genes that make a difference in patient care to now almost ten different biomarker abnormalities that completely change the type of therapy that's appropriate for the patient.
It allows you to match a therapy to the patient, often with highly effective results for these patients with low toxicity.
Nowadays, biomarker testing should be the standard of care before any treatment is chosen for any stage of lung cancer. We're not operating in a world of one-size-fits-all anymore where everybody gets the same therapy.
The results of biomarker testing can change therapy from chemotherapy alone to chemotherapy with immunotherapy, immunotherapy alone, or targeted therapies alone. These are all expensive therapies, but when matched to the right patient and the right tumor are highly effective and that matching requires biomarker testing and knowledge and action on the results before starting systemic therapy.
Why is it then that more than half of cancer patients have not received biomarker testing or are unsure if they have?
I think there's a lack of education of both oncologists and patients of the importance of biomarker testing.
You can understand how stressful a diagnosis like this is. Patients are learning a whole new vocabulary, they're meeting a bunch of doctors they've never seen before and trusting them with their lives.
They want therapy right away, they don't want to wait.
The problem with that is that randomly choosing a therapy for a patient without biomarker testing often results in choosing the wrong therapy or even a harmful therapy.
What often happens is that patients rush into therapies without biomarker testing or the doctor doesn't wait for the results to come back for biomarker testing because of the stress associated with the diagnosis. So, I think it's important for all the healthcare providers to emphasize to the patient that it's more important to wait a few days or weeks for results and choose the right therapy than to choose a random therapy that may be the wrong one for you.
However, there are multiple barriers at different levels. There's the barrier of burden on the practitioner to send another test to wait for the result; It's another test that has to be done and doctors these days are busy. There's a psychological barrier with patients wanting to start treatment right away. There's barriers in the quality of biopsies. There's barriers in educating healthcare professionals.
How can healthcare providers ensure that more patients receive the necessary biomarker testing?
It begins with the diagnosis of lung cancer. Practitioners should work together with the people doing the biopsies, the surgeons, the pulmonologists, the interventional radiologists to make them aware of the importance of getting an adequate biomarker biopsy for biomarker testing. At our place, these people who do the biopsies are generally not the ones that do the treatment of the cancer, but they are well informed of the importance of biomarker testing. When they get the result back from a biopsy, they will order the biomarker testing directly so that by the time the treating physician sees the patient, the results are available for decision making. To me, it's important to change our standard practice so that it's not the medical oncologist ordering the test, but rather the people doing the biopsy and that adequate biopsies are performed to get this done in time so you can get therapy started in a timely manner.
What impact can the approvals of targeted therapies for early-stage lung cancer have on patient outcomes?
Both EGFR-targeted and ALK-targeted therapies result in dramatically improved progression-free survival after surgery. It's often thought that if you have surgery, the cancer's gone and the problem is over, but more than half of the people who have what is thought to be a complete surgical resection eventually experience the return of the cancer, and usually metastatically. These therapies reduce your chance of recurrence in the years after surgery by around fivefold, which is huge.
When I started treating lung cancer over 35 years ago, all we had was chemotherapies. We didn't even have effective nausea medications, so these patients suffered terribly. On average, chemotherapies improved survival by only a couple of months. They're friendlier and better tolerated now, but the newer targeted therapies and immunotherapies have virtually no side effects or just low-grade side effects and are dramatically effective at shrinking the cancer and improving quality of life.
How do you address concerns about the cost and accessibility of biomarker testing for patients?
The costs and accessibility have been getting better over time, though nothing in medicine is cheap. These tests can cost a few thousand dollars in the US, but they make such a difference in not only the type of therapy you choose but in the probability of response and the quality of life of the patient, that the cost-benefit is huge. These biomarker tests generally cost less than a month of targeted therapies, yet it totally transforms the outcomes for the patient. To me, it's one of the best investments that can be made in the treatment of a lung cancer patient, and it should be available to everyone.
How can collaborations between research institutions, healthcare providers, and pharmaceutical companies enhance the development and implementation of biomarker-driven treatments?
A lot of these biomarker-driven tumors are uncommon, in the range of 1% or less. A general practice oncologist may see one of these cases every other year, so it requires collaboration between institutions, nationally and internationally, to identify these patients and test new drugs. There are cooperative groups and multi-site pharma studies that are open in many institutions, sometimes over 100 across the country, in order to identify patients with these rare abnormalities in their tumors.
How do you foresee the future of personalized cancer evolving, especially with advancements in biomarker testing?
Every day we have patients who dramatically benefit from biomarker testing. When I started in this business, the average survival for a metastatic lung cancer patient was four to six months from diagnosis to death. If you gave them chemotherapy, you may be extending their life by six or eight weeks at the expense of serious toxicity, losing their hair, nausea and vomiting. Today we get people who are desperately ill, even with metastases to the brain who start on this one pill a day and within months are back to normal and go back to work. And we see this every day.
We are regularly adding new vulnerabilities that have been discovered in cancers to the list of biomarkers that are needing to be tested. One of the more recent was KRAS-G12C, which was untargetable for many years, but we now have several drugs that target that mutation. As time goes on, it will be even more crucial to do biomarker testing. We really need better biomarkers to match immunotherapies to patients like we have been effective in doing with the targeted therapies. I expect in the future this will become even more complex, but will bring better outcomes for our patients.
