Additional Guidelines Around Biomarkers Could Improve Adjuvant Treatment of Early-Stage NSCLC

Therapeutic options for patients with advanced-stage lung cancer have exponentially increased in the past decade or so, particularly with the advent of targeted therapies and immuno-oncology, explained Jacob Kettle, PharmD, BCOP, director and pharmacy manager at Ellis Fischel Cancer Center Service Line, University of Missouri Health Care in Columbia, during a Pharmacy Times clinical forum. Kettle explained further that there’s a significant unmet need for adjuvant-based therapy for patients with early-stage non-small cell lung cancer (NSCLC; stages I, II, and III).

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It all starts with the diagnosis, Kettle said. According to national literature estimates, 25% to 30% of patients are diagnosed early at the resectable stage, but surgical resection to remove the tumor is usually effective for only stage I disease. “We still don’t do a great job of diagnosing NSCLC early,” Kettle said during the forum.

However, testing biomarkers and building effective lung cancer clinical pathways could improve the adjuvant immunotherapy and targeted treatment options that are available to patients with resected early-stage NSCLC. Biomarkers are medical signs—often identified via molecular testing—that are predictive of a disease pattern, or the likelihood of a disease responding to a certain kind of treatment. Identifying biomarkers for patients allows the oncology pharmacist to give patients the drugs that will most directly benefit them, Kettle explained.

Biomarker testing used to be reserved for patients who have later-stage NSCLC, but updated National Comprehensive Cancer Network (NCCN) recommendations include eligible patients with resectable, early-stage, locally advanced NSCLC who have received adjuvant chemotherapy.

Clinical forum panelist Kelsey Schildknecht, PharmD, BCOP, a clinical pharmacist at TriHealth Cancer Institute in Cincinnati, Ohio, most often witnesses testing done after the patient’s initial treatment and prior to adjuvant treatment. Panelist Lauren Gilmer, PharmD, BCOP, a specialty clinical coordinator at TriHealth and an adjunct assistant professor at the University of Cincinnati, said testing orders are usually oncologist dependent.

Common biomarkers in lung cancer include EGFR, ALK fusion genes, MET exon 14 skipping mutations, ROS1, and immunotherapy biomarker PD-L1, the panelists explained. However, in some instances, biomarkers can actually make caring for patients more difficult because biomarkers can indicate certain disease mutations or states, but there are not enough definitive treatment guidelines available—often because of the fast pace of the field and new treatment developments—that will help to inform the care team about how (or what) immunotherapies or targeted treatments to apply, in what order, and based off what particular biomarker.

When it comes to biomarkers and early-stage NSCLC treatment options, “the pace of information [sometimes] moves faster than our ability to process it or know how to use it to apply to care,” Kettle said.

Gilmer suggested that it would be beneficial to have more definitive treatment guidelines that discuss how to apply the resulting biomarker data toward choosing an adjuvant therapy. She recalls how the emergence of KRAS inhibitors for KRAS mutations had her team questioning how exactly to approach treatment for patients because the treatment was so new. Schildknecht added that any guidelines developed to help with these decisions should also address the question of what is best and when.

Clinical pathways could provide this better means of creating high-quality, predictable, expected outcomes, according to Kettle. Clinical pathways transform recommended guidelines into processes of care. “One of the most unique things about practicing oncology now…is we have so much choice,” he said. “It’s a great problem to have, but it also makes it difficult to achieve those predictable, repeatable results.”

The merit of treating a patient with a clinical pathway is that it provides a “road map” to care, said Nate Miller, PharmD, BCPS, BCOP, a clinical pharmacist at TriHealth Good Samaritan Hospital. But pathways can be nuanced or even “too good to be true,” Miller said. Additionally, choosing subsequent therapies can become even more difficult. If a patient relapses or has a complication after taking one of the first-line adjuvant therapies recommended on a pathway, it can be difficult to determine what to do for the next round of treatment.

When building a clinical pathway, the health care team should prioritize survival and safety, according to Gilmer. It’s also important to be flexible with the treatment plan, as insurance, drug cost, or patient values and desires could drive a different course of action for treatment. This is also why the provider should not oversell 1 type of therapy, Kettle explained.

Furthermore, the role of the pharmacist is crucial in the NSCLC setting. The oncology pharmacist can manage financial or inpatient care or run full clinical checks to ensure that patients get their medication and can tolerate it. Pharmacists can also have a role in educating the patient and understanding their adverse events (AEs) to help improve quality of life. Gilmer also suggested that it is valuable for the pharmacist to be informed about the patient’s life outside their health and disease management, as personal habits and practices can impact adherence. Further, Miller said the pharmacist has a responsibility to remind the patient of additional therapeutic needs.

The current standard of care for early-stage NSCLC is platinum-based doublet therapy, but rather than patients going through multiple rounds of chemotherapy intervention, biomarkers allow patients to have effective and personalized adjuvant treatment options at their disposal—in particular, targeted treatments and immunotherapy, Kettle said. However, not every adjuvant option is fit for every tumor type. For instance, atezolizumab (Tecentriq; Genentech) is an immunotherapy drug that would be used for someone with a resected early-stage NSCLC that has a varying degree of PD-L1 expression. But if the patient were identified as having an early-stage EGFR-positive tumor—with said tumor being resected and the patient treated with chemotherapy—they should not receive adjuvant immunotherapy after chemotherapy, as EGFR-mutated tumors do not respond well to it, Kettle explained.

The NCCN panel also recommends reslizumab (Cinqair; Teva Pharmaceutical Industries Ltd) as an adjuvant therapy option for eligible patients who have “complete resected stage IIB, IIIA, stage IIIB, or high-risk stage IIA [tumor] with PD-L1 expression greater than 1%, who are negative for certain biomarkers such as EGFR and who previously received adjuvant chemotherapy based on clinical trials and FDA approval,” Kettle said.

Clinical pathways could then lead to the creation of more standardized and multidisciplinary care plans for administering adjuvant treatment to patients with early-stage NSCLC based on biomarker data, AEs, patient values, and other factors. “There’s no shortage of advancements, [and] the role for pharmacists and oncology is only going to continue to expand,” Kettle said. “It’s an exciting time to be in practice.”