“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.”
“Bristol-Myers Squibb CompanyBMY-0.86% today announced safety and efficacy data from a Phase 1/2 study of urelumab in combination with Opdivo (nivolumab) in patients with hematologic and solid tumors, including biomarker analyses by level of PD-L1 expression. The combination of urelumab and Opdivo showed encouraging efficacy among 46 evaluable melanoma patients with an objective response rate (ORR) of 50% (23/46 with 18 confirmed and 5 unconfirmed). ORR was a secondary endpoint as measured by Response Evaluation Criteria In Solid Tumors (RECIST). Similar response was seen in both PD-L1 positive and PD-L1 negative melanoma patients, with ORR of 50% (10/20) and 47% (8/17) in those with greater-than or equal to 1% and <1% PD-L1 expression, respectively. Among the other cohorts (n=78), one non-small cell lung cancer (NSCLC) patient and one squamous cell carcinoma of the head and neck (SCCHN) patient had an objective response. In the full patient population (n=138), no significant added toxicity was observed with urelumab in combination with Opdivo over Opdivo monotherapy. These data were presented at an oral presentation (poster number 239) at the Society for Immunotherapy of Cancer (SITC) 31 Annual Meeting on November 12 at 10:40 a.m. EST in National Harbor, Maryland.”
“Although nivolumab (Opdivo) has demonstrated a clear survival advantage compared with chemotherapy in patients with progressive non–small cell lung cancer (NSCLC) who express PD-L1 in their tumor cells, the same cannot be said for those who are PD-L1–negative.
“As a result, researchers are seeking to elicit antitumor activity in a broader range of patients, notably through a multiarm trial evaluating the PD-1 inhibitor along with combinatorial approaches.
“CheckMate-227 (NCT02477826) is a phase III, open-label, randomized trial for patients with chemotherapy-naïve stage IV or recurrent NSCLC. The trial will enroll patients into separate groups according to PD-L1 expression status (≥1% or <1%).”
“Merck & Co has won U.S. approval to market its immunotherapy Keytruda for use in previously untreated lung cancer patients two months ahead of schedule, making it the only such drug cleared for first-line treatment.
“The green light from the Food and Drug Administration (FDA), announced by the U.S. drugmaker late on Monday, confirms Merck’s leading position in the hot area of medicines that fight tumors by harnessing the body’s immune system.
“Keytruda’s latest approval is for treating first-line metastatic non-small cell lung cancer (NSCLC) in patients with high-levels of a protein called PD-L1, which makes them more receptive to immunotherapy.”