A late afternoon extended education session on the first day of the 2017 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, was a discussion on the state-of-the-art uses for immunotherapy in the management of non-small cell lung cancer (NSCLC).
A late afternoon extended education session on the first day of the 2017 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, was a discussion on the state-of-the-art uses for immunotherapy in the management of non-small cell lung cancer (NSCLC). Oncologists shared their experiences with the management of toxicities resulting from immunotherapy, and also discussed the role of immunotherapy in specific patient populations.
Edward B. Garon, MD, director of the thoracic oncology program and associate professor of medicine at the David Geffen School of Medicine at University of California Los Angeles, spoke about using checkpoint inhibitors, primarily programmed death-1 (PD-1) inhibitors, in first-line therapy and sequencing these agents.
Garon discussed results from Keynote-024, a phase 3 randomized controlled trial that compared pembrolizumab as frontline therapy, compared with platinum-based chemotherapy, in patients diagnosed with programmed death ligand-1 (PD-L1)—expressing advanced NSCLC (50% PD-L1 expression threshold). The primary study endpoint was progression-free survival (PFS). Despite patients who crossed over from pembrolizumab to chemotherapy, overall survival increased .
Checkmate-026, which had a similar study design, compared first-line single agent nivolumab versus chemotherapy. Crossover was allowed and PFS was the primary endpoint. The main difference was that the PD-L1 expression cut-off was set at 5%, which would include a much broader patient population.
Nivolumab, however, failed in the frontline setting compared with chemotherapy. “Overall survival (OS) was not different in the 2 arms,” Garon said.
He lined up a series of differences to explain the differential results:
Garon also drove home the point of a tumor’s mutation burden: “Higher the mutation burden, greater is the benefit,” he said.
The take-home messages from Garon’s presentation were:
Melissa Lynne Johnson, MD, associate director of lung cancer research at Sarah Cannon Research Institute, addressed the conundrum of choosing a suitable immunotherapy agent.
She explained that PD-1 and PD-L1 inhibitors are monoclonal antibodies. The interesting thing is that different PD-1 inhibitors bind different faces of the PD-L1 protein. “They also block different protein-protein interactions,” which might result in differences in patient responses based on which drug is administered.
Variability also arises from IGG isotypes and antibody-dependent cell-mediated cytotoxicity (ADCC). “Avelumab is the only immunotherapy drug that has retained its ADCC function, compared with nivolumab, durvalumab, pembrolizumab, and atezolizumab,” Johnson said.
Another source of variability in response arises from the PD-L1 assay used to assess protein expression.
Patient adverse events (AEs) associated with the treatment have varied, Johnson said. The rate of AEs has hovered around 76% for nivolumab, Johnson said, much higher than pembrolizumab (67.5%), atezolizumab (65%), durvalumab (60.6%), and avelumab (67%).
The survival data in the second-line setting has found that median OS is 12.2 months for nivolumab, compared with docetaxel for non-squamous NSCLC; 10.4 months with pembrolizumab, compared with 8.5 months with docetaxel; and 13.8months for atezolizumab, compared with 9.6 months.
In the first-line setting, however, nivolumab has lagged behind pembrolizumab, Johnson showed. The median progression-free survival for nivolumab is 4.2 months for nivolumab, compared with 5.9 months for chemotherapy. Pembrolizumab, on the other hand, has a median PFS of 10.3 months. While median OS for nivolumab is 14.4 months, it has not yet been reached for pembrolizumab.
Johnson drove home the point that cost vs convenience is another question that both physicians and patients are concerned with. Nivolumab is administered every 2 weeks (both 240 mg and 3 mg/kg doses) and costs about $21,990 for a 6-week treatment. Pembrolizumab is administered once in 3 weeks (both 240 mg and 2 mg/kg doses) and costs about $21,662 over 6 weeks.
She proposed the idea of evaluating these agents over a long treatment interval, to both lower costs and lower the inconvenience of frequent administration for patients.
Johnson summarized her presentation by saying that in the first-line setting, understanding the role of the tumor microenvironment might help understand the differences in patient response, as will identifying additional biomarkers. “Until then, dosing schedule and cost will continue to play a significant part in oncologists’ decision making,” she said.
Lack of Mutations Associated With Favorable Prognosis in MPN-U
April 25th 2024While the Dynamic International Prognostic Scoring System and bone marrow blasts may predict overall survival, the lack of certain mutations is also associated with a better prognosis for myeloproliferative neoplasm, unclassifiable (MPN-U).
Read More
Examining Low-Value Cancer Care Trends Amidst the COVID-19 Pandemic
April 25th 2024On this episode of Managed Care Cast, we're talking with the authors of a study published in the April 2024 issue of The American Journal of Managed Care® about their findings on the rates of low-value cancer care services throughout the COVID-19 pandemic.
Listen
HOPE-CAT Can Identify Maternal Cardiovascular Risk 2 Months Earlier Than Doctors, Study Says
April 25th 2024In a retrospective study, the machine learning tool was able to screen for potential risks of cardiovascular disease nearly 60 days before the patient's medical record showed any signs of a related condition or before they were officially diagnosed or treated for it.
Read More
Data Back Neoadjuvant Combo vs Chemo Alone for Early-Stage NSCLC
April 24th 2024For patients with early-stage non–small cell lung cancer (NSCLC), combining neoadjuvant immune checkpoint inhibitors and platinum-based chemotherapy improves 2-year outcomes over chemotherapy alone, suggest findings of an extensive literature review and meta-analysis.
Read More