The future of adjuvant and neoadjuvant treatments for early-stage resectable non-small cell lung cancer will involve identifying biomarkers to determine which patients can benefit from perioperative immunotherapy and targeted therapy, according to a recent review published in JCO Oncology Practice.
While cisplatin-based platinum-doublet adjuvant chemotherapy following surgical resection has been standard of care for some time in early-stage resectable NSCLC, perioperative immunotherapy and targeted therapy for patients with defined biomarkers have shown promise, according to Dipesh Uprety, MD, an assistant professor within the department of medical oncology at the Barbara Ann Karmanos Cancer Institute, and Howard Jack West, MD, a thoracic oncology specialist and an associate professor in medical oncology at City of Hope Comprehensive Cancer Center, said. “[P]erioperative immunotherapy and targeted therapy have recently taken their place as potential additions to the current standard of care for patients with stage IB-IIIA NSCLC on the basis of a series of positive trials that offer a new range of options,” the researchers wrote.
Since data from the ADAURA trial established adjuvant osimertinib significantly improved disease-free survival in patients with stage IB-IIIA NSCLC who have EGFR-positive disease for up to 3 years, new data has emerged showing the disease-free survival (DFS) benefit declines after treatment is stopped. This raises the question of whether adjuvant osimertinib will need to be continued indefinitely in these patients, the authors explained.
Immunotherapy has been used in neoadjuvant and adjuvant regimens, with improvements in DFS seen with agents such as adjuvant atezolizumab in patients with PD-1, PD-L1 positive stage II-IIIA NSCLC, and adjuvant pembrolizumab in stage IB-IIIA NSCLC. In other cases, the best treatment is unclear, such as in deciding between neoadjuvant chemotherapy/nivolumab or adjuvant atezolizumab after chemotherapy in patients who do not have a sensitizing driver mutation, based on the authors’ observations.
Key questions to answer in the future are determining how each component of treatment impacts benefit, what the optimal treatment duration for each is, and what decision to make when considering minimal residual disease in weighing treatment options, the authors noted. “[O]ur current practice continues to evolve as we await more mature data from these studies and additional results that promise to help us better refine our understanding of an optimal duration of treatment and identify a reliable surrogate end point for OS,” Uprety and West wrote. “At the same time, there is an urgent need for biomarkers to help us recognize which patients will truly benefit while others may be safely observed.”
In a related editorial, Millie Das, MD, of the department of medicine and division of oncology at Stanford University, said recent advances in immunotherapy have given clinicians “greater options to offer a better chance at cure.” The future of immunotherapy will also have to consider autoimmune side effects, which can be unpredictable and have “the potential for harm, especially in patients who may otherwise be cured.”
“The one size fits all approach will not work, and treatment decisions will need to be individualized and personalized on the basis of tumor characteristics (PD-L1 status and presence of a driver mutation) and a patient’s risk tolerance, carefully weighing the risks of additional therapy with the risks of disease recurrence,” Das concluded.
--
Disclosures: Authors declared financial ties to drugmakers. See full study for details. ADAURA was supported by AstraZeneca.
Photo Credit: Getty Images.
