“Improvements in OS, but not PFS, indicate that maintenance treatment with pembrolizumab may benefit a subset of patients with small cell lung cancer, and biomarkers are needed to identify individuals in whom pembrolizumab may be effective, according to findings presented at the ASCO Annual Meeting.
” ‘The standard of care for these patients – 4 to 6 cycles of platinum plus etoposide – has not changed in the United States in the last 30 years,’ Shirish Gadgeel, MD, of the Karmanos Cancer Institute in Detroit, said during a presentation. ‘Despite a high response rate with this therapy, overall outcomes for these patients are quite poor. There is a need to identify other agents that can provide benefit in these patients.’ ”
“Atezolizumab (Tecentriq) monotherapy produced substantial response rates as first-line or subsequent treatment in patients who had advanced non-small cell lung cancer (NSCLC) with confirmed programmed cell death ligand 1(PD-L1) expression, reported the phase II BIRCH trial.
“Atezolizumab therapy produced a 22% objective response rate in first-line treatment, 19% in second-line, and 18% in third-line or higher in patients with PD-L1 expression on ≥ 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), according to Enriqueta Felip, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, and colleagues. Patients with the highest levels of PD-L1 expression — TC3 or IC3 — had better objective response rates: 31% in first-line, 26% in second-line, and 27% third-line or higher.”
“Findings from a phase III clinical trial for advanced lung cancer patients could help oncologists better predict which patients are likely to receive the most benefit from immunotherapy as a first-line treatment based on the unique molecular characteristics of their tumor, according to a new study reported by a global team led by David Carbone, MD, PhD, of The Ohio State University Comprehensive Cancer – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
“In this study, researchers compared the effectiveness of the immunotherapy drug nivolumab (pronounced ‘nye VOL ue mab,’ marketed at Opdivo), with standard-of-care chemotherapy in 541 patients with previously untreated or recurrent non-small cell lung cancer (NSCLC) that expressed PDL-1 antibodies.”
“Updates to the National Comprehensive Cancer Network (NCCN) guidelines for the management of advanced non–small cell lung cancer (NSCLC) stress the importance of multiplexed biomarker testing at diagnosis to aid in the selection of appropriate first-line and subsequent lines of therapy, said presenters at the 2017 NCCN Annual Conference.
“The latest version of the guidelines recommends that PD-L1, in addition to molecular analysis, be employed as a biomarker to direct initial therapy, with ≥50% expression established as the threshold for a positive result. The PD-L1 test ‘decides whether a patient has enough of the marker to warrant initial immunotherapy,’ said presenter Gregory J. Riely, MD, PhD.”
“Long-term survival in non-small cell lung cancer (NSCLC) exceeded historical standards among patients treated with the immune checkpoint inhibitor nivolumab (Opdivo), according to a study reported here.
“The 129 patients in the study had an estimated 5-year overall survival of 16%. Among those with measurable levels of PD-L1 expression, 5-year survival ranged as high as 43%.”
“UCLA scientists have discovered that people with cancers containing genetic mutations JAK1 or JAK2, which are known to prevent tumors from recognizing or receiving signals from T cells to stop growing, will have little or no benefit from the immunotherapy drug pembrolizumab. This early-stage research has allowed them to determine for the first time why some people with advanced melanoma or advanced colon cancer will not respond to pembrolizumab, an anti-PD-1 treatment.
“The study, led by Dr. Antoni Ribas, director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program, also found that JAK1 or JAK2 genetic mutations led to a loss of reactive PD-L1 expression. PD-L1 is an immune biomarker expressed on tumor cells and pembrolizumab requires an abundance of it to effectively attack cancer cells.”
“Immunotherapy is quickly becoming a mainstay in the frontline setting for the treatment of patients with metastatic non–small cell lung cancer (NSCLC).
“In October 2016, the FDA approved the PD-1 inhibitor pembrolizumab (Keytruda) as a first-line treatment for patients with metastatic NSCLC whose tumors have at least 50% PD-L1 expression and who do not harbor EGFR or ALK mutations.”
“The FDA granted priority review to a supplemental biologics license application for pembrolizumab in combination with chemotherapy for first-line treatment of patients with metastatic, nonsquamous non–small cell lung cancer, according to the drug’s manufacturer.
“The application seeks approval of pembrolizumab (Keytruda, Merck), an anti–PD-1 therapy, in combination with pemetrexed and carboplatin regardless of patients’ PD-L1 expression, provided they have no EGFR or ALK mutations.
“The FDA is expected to make a decision by May 10.”
“Recent research suggests that the presence of PD-L1–positive and CD8+ cells may be useful for predicting responses in patients with non-small cell lung cancer (NSCLC) who have been treated with durvalumab (MEDI4736).
“Sonja Althammer, PhD, presented research on the association between improved survival rates to treatment with durvalumab and high CD8+ and PD-L1+ cell densities during a late-breaking abstract session at the Society for Immunotherapy of Cancer (SITC) 21st Annual Meeting & Associated Programs.”