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Title Options:
- Tailoring ROS1+ NSCLC Treatment: The Role of Biomarker Testing (65 characters)
- Biomarkers in ROS1+ NSCLC (25 characters)
- Targeted NSCLC Care: Biomarker Testing (38 characters)
- Personalized NSCLC Care: Biomarker Testing (42 characters)
Outline:
- Intro:
- High-level overview of biomarker testing and the importance of early detection
- High-level overview of what the 2024 NCCN guidelines say on biomarker testing.
The American Lung Association suggests thinking of DNA like words in a book, where errors can change meaning, leading to uncontrolled cell growth and cancer. Some lung cancer treatments target these DNA changes directly, causing fewer side effects by focusing on cancer cells. Biomarker testing looks for DNA mutations, additions, deletions, or rearrangements, helping to inform treatment options.
This testing, also called molecular or genomic testing, can reveal specific abnormalities in the tumor’s DNA and protein levels, guiding targeted therapies or immunotherapy. Not all lung cancers have treatable biomarkers, so discussing biomarker testing and treatment options with your patients is essential.
Why Biomarker Testing?
According to the NCCN, lung cancer incidence has been decreasing annually, mainly due to reduced cigarette smoking, which is estimated to cause 81% of lung cancer deaths in 2024. Advances in screening, minimally invasive techniques, radiation therapy, targeted therapies, and immunotherapies have improved survival rates, particularly for patients with non-small cell lung cancer (NSCLC) who are eligible for these new treatments. Biomarker testing is essential for guiding treatment and improving outcomes, especially in advanced or metastatic NSCLC.
Several biomarkers have emerged as crucial for predicting and assessing prognosis in NSCLC. Predictive biomarkers indicate therapeutic efficacy, while prognostic biomarkers suggest patient survival independent of treatment. The NCCN Panel recommends molecular and immune biomarker testing for patients with NSCLC to determine eligibility for targeted therapies or immunotherapies, which have shown improved survival rates. Testing is advised for patients with stage IV NSCLC and resectable early-stage NSCLC. Key predictive biomarkers include ALK, BRAF, EGFR, HER2, KRAS, MET, NTRK, RET, ROS1, and PD-L1.
Broader molecular profiling is encouraged to identify rare driver mutations for targeted therapies. Further, plasma ctDNA testing can be used in specific circumstances, though it should not replace tissue diagnosis. Laboratories should also use validated methods for biomarker testing to ensure accurate and actionable results.
Benefits of Biomarker Testing in ROS1+ NSCLC
Physician’s Weekly (PW) spoke with Debora Bruno, MD, associate professor of medicine at Case Western Reserve University and lead of the medical oncology thoracic group at University Hospitals Senet Cancer Center to better understand the importance of biomarker testing in guiding treatment decisions for patients with NSCLC with ROS1+ mutations.
She explains that next-generation sequencing (NGS) can test tissue biopsies and circulating tumor DNA (CT DNA) from blood draws. Dr. Bruno also highlights the importance of considering factors such as the presence of brain metastasis when tailoring a treatment plan and the role of biomarker testing teams in identifying and managing ROS1+ NSCLC.
PW: Could you speak to the significance of biomarker testing in guiding treatment decisions for patients with NSCLC ROS1+ mutations and how that contributes to precision medicine?
Dr. Bruno: Biomarker testing is key in determining the best therapies for patients with NSCLC, not only in the metastatic setting but also in early-stage and locally advanced diseases. We have nine subpopulations of NSCLC subtypes with different genomic alterations for which we have FDA-approved therapies available. It’s important for us to perform multiplex testing for these patients, and we need to test for all alterations while using the specimen in the best way possible without exhausting it.
How do we go about that? By using NGS—where multiple genomic alterations of the cancer are tested in parallel. That way, the specimen can be utilized most of the time, not exhausted with only one or two tests.
We can test both the tissue and biopsy obtained from these patients and perform liquid biopsies, circulating tumor DNA, or CT DNA, which is a blood draw. You get a blood draw from your patient and go about sequencing the DNA the tumor is shedding into the circulation.
How does your practice integrate biomarker testing into the management of NSCLC?
We test upfront. Before deciding the best therapy available for the patient, we test everyone in the first line setting at our institution. We perform reflex testing. After the patient is diagnosed with NSCLC, the specimen that biopsy is signed out by the pathologist as NSCLC and red-flagged before moving to the molecular pathology lab, where NGS takes place in-house. We have a very nice molecular pathology lab that tests in-house and performs a focused NGS test focusing on 60 genomic alterations. So not only the ones for which we have FDA-approved therapies, but also genomic observations that help us understand the biological behavior of that disease, how immunotherapy may help that patient or not, and so forth.
Many of us also send liquid biopsies when we see the patients in the clinic for the first time. We want to have a bigger understanding of what’s going on and see what the tumor is shedding. But sometimes, for one reason or another, you may not have the NGS test result from the biopsy that was obtained. Sometimes, the biopsy is insufficient, and the patient doesn’t want to undergo another procedure. So, we do liquid testing in those circumstances, too. One thing that is important to highlight is that we also perform PDL testing in all our patients with non-small cell lung cancer. It’s not genomic sequencing; it’s not part of the NGS testing platform. It’s an immunohistochemistry test, but it is important and valuable in helping us understand how immunotherapy may help our patients. And then, of course, if the patient has genomic alterations, we give them targeted therapies, especially in the metastatic setting. If they progress on that targeted therapy later, sometimes we biopsy the patient or send another liquid biopsy to understand if there are new genomic observations that we can target with another type of targeted therapy or combine targeted therapies to best manage the patient after that patient fails the first line treatment that we provide.
Genomic and biomarker testing are incorporated into our practice to decide on the best standard of care and provide patients with access to clinical trials. So, this is something also that we do. We have a molecular tumor board that meets briefly twice a week with a navigator, molecular pathologist, and a medical oncologist to review the testing results of all available patients. Based on those testing results, the genomic profile of the tumor, and the PD-L1 levels, we suggest clinical trials to patients, and that’s incorporated into the electronic medical record of that patient. We also have a navigator who reaches out to the providers and the treating oncology providers throughout the network. Our network is a hybrid academic community practice network. They reach out to the navigator and the oncologist to let them know the patient has this genomic alteration; these are the clinical trials available for your patient. If the patients are not interested in the clinical trial, this is the patient’s standard of care option.
What factors do you consider when tailoring a treatment plan for this patient population?
It’s not only about the type, presence, or absence of an actionable genomic alteration for which we may have a targeted therapy available or the levels of PD-L1 that immunohistochemistry tests we perform on patients to best decide on immunotherapy and chemotherapy. It’s also about understanding the patient’s disease burden.
For patients who have a lot of disease burden, many metastases, despite having or seeming to have tumors that will respond very well to immunotherapy, may be best treated with chemotherapy and immunotherapy. In that setting, we consider the comorbidities of the patients. Some patients have problems with kidney function, who have problems with functional status for which we must tailor the therapies available, or have issues with peripheral neuropathy and so forth.
It’s always about looking at the big picture and discussing the pros and cons of each therapy that is indicated for that specific case, discussing the potential side effects with the patient, how often infusions will be given, how often the patient will have to come for testing and for spend time with us right in the infusion chair if infusions are indicated.
All those factors, including the presence of brain metastasis, must be considered because you must also understand that as medical oncologists, we must coordinate the care with other disciplines that will be taking care of that patient. Patients with brain metastasis may require seeing a radiation oncologist, and so on. Coordinating care is always an important challenge, but of course, the center of that is always the patient.
How do you specialize biomarker testing teams to enhance the identification and management of patients with ROS1+ NSCLC?
Considering that we now have three FDA-approved therapies to treat ROS1 fusions or rearrangements, we must identify the ulceration before using those medications. The tissue procurement teams are the people who obtain biopsies, be it the interventional radiologists or the pulmonologist who performs bronchoscopies with endobronchial ultrasounds or navigational bronchoscopies, are key to obtaining enough tissue that can be utilized for testing. This tissue, which is non-small cell, will be used for diagnosis. After the pathologist completes initial testing, we must have enough tissue to do more testing, such as the NGS testing, PDL1, and so forth. It’s important that coordination occurs and that the tissue procurement teams know they need to obtain enough tissue for testing.
It is also important to note that the pathology team understands the need not to exhaust the tissue that was obtained with unnecessary immunohistochemistry testing. We know we need very few IHC or immunohistochemistry tests to determine if it’s an NSCLC, an adenocarcinoma, or a squamous cell carcinoma. We shouldn’t be doing a lot of esoteric IHC testing for those patients to avoid exhausting the biopsy specimen. This is key.
Finally, knowing that the pathology team needs to know that patients with NSCLC nowadays need to be tested for NGS. In conjunction with pathology, the reflex testing approach is key in our institution. We’re lucky to have a molecular pathology lab that plays a vital role—the turnaround time is fast. After the results are out there, it’s important to communicate that the test results are in and make sure that the treating oncologist understands those results and how to best utilize them in managing the patient.
Choosing the right standard of care therapy for the patients with ROS1 alterations is vital, and understanding that these patients are best treated with targeted therapies, not really with immunotherapy or chemotherapy in the metastatic setting.
