“Combined immunotherapy with two checkpoint inhibitors — nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) — has shown ‘clinically meaningful’ efficacy in patients with asymptomatic, untreated melanoma metastases to the brain, according to a report regarding new data from the CheckMate 204 open-label phase 2 study.
” ‘Although current practice is to start with surgery, stereotactic radiotherapy, or both followed by immunotherapy or targeted agents, our results support the initiation of immunotherapy to achieve prompt control of both extracranial and brain metastases,’ write the authors.”
“Today, nivolumab (Opdivo) received approval from the U.S. Food and Drug Administration (FDA) for patients with metastatic small cell lung cancer (SCLC) whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy. Approval for this indication has been granted under accelerated approval based on overall response rate and duration of response.
“This approval for nivolumab had been granted Priority Review from the FDA. It was based on data from the SCLC cohort of the ongoing phase I/II CheckMate-032 study evaluating nivolumab monotherapy in patients who experienced disease progression after platinum-based chemotherapy.”
“The FDA has accepted a supplemental biologics license application (sBLA) for the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the frontline treatment of patients with advanced non–small cell lung cancer (NSCLC) with tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb), according to Bristol-Myers Squibb (BMS), the manufacturer of both immune checkpoint inhibitors.
“The sBLA is based on findings from the phase III CheckMate-227 trial presented at the 2018 AACR Annual Meeting and published in the New England Journal of Medicine, in which the 1-year progression-free survival (PFS) rate was 43% for patients with high TMB (≥10 mut/Mb) assigned to the immunotherapy combination compared with 13% for those assigned to platinum-doublet chemotherapy. The median PFS was 7.2 months versus 5.5 months, respectively, representing a 42% reduction in risk of disease progression or death (HR, 0.58; 97.5% CI, 0.41-0.81; P <.001).”
“Researchers at the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy (BKI) released a study investigating the use of combination checkpoint immunotherapy in the treatment of a lethal form of advanced prostate cancer. The study suggested a genetic subset of prostate cancer may benefit from this form of immunotherapy.
“The combination of nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) reduced the risk of progression or death by 52% compared with standard platinum doublet chemotherapy for patients with metastatic PD-L1–negative, tumor mutation burden (TMB)-high non–small cell lung cancer (NSCLC), according to findings from the phase III CheckMate 227 trial presented at the 2018 ASCO Annual Meeting.
“In the PD-L1–negative (<1% expression), TMB-high (≥10 mutations/megabase) subgroup, regardless of histology, median progression-free survival (PFS) with nivolumab/ipilimumab was 7.7 months compared with 5.3 months for chemotherapy and 6.2 months for nivolumab and chemotherapy. The 1-year PFS rate was 45% with nivolumab/ipilimumab compared with 27% for nivolumab/chemotherapy and just 8% for chemotherapy.”
“Patients with surgically resected stage III or stage IV melanoma at high risk for recurrence maintained longer RFS after adjuvant treatment with nivolumab then standard ipilimumab, according to long-term efficacy results from the CheckMate 238 clinical trial presented at ASCO Annual Meeting.
“‘These more mature data continue to demonstrate durable clinical benefit with nivolumab and further support its use for resected stage III or IV melanoma,’ Jeffrey S. Weber, MD, PhD, deputy director of Perlmutter Cancer Center at NYU Langone Health, said during his presentation.”
Immune checkpoint inhibitor drugs that target the proteins PD-1 and PD-L1 are by now well established in the treatment of non-small cell lung cancer (NSCLC). In 2015, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo), an anti-PD-1 drug, for treatment of patients with metastatic NSCLC who progressed or relapsed after platinum-based chemotherapy. Atezolizumab (Tecentriq), an anti-PD-L1 drug, was approved in 2016 for treatment of NSCLC patients in the same situation. In October 2016, the FDA approved Pembrolizumab (Keytruda), a competing anti-PD-1 antibody, as first-line treatment in metastatic NSCLC patients whose tumors have high expression levels of the PD-L1 protein.
With these approvals, the stage was set to move these drugs into combination treatments that may increase their efficacy. Not surprisingly, combinations with chemotherapy have now been explored, among other possibilities. Continue reading…
“Bristol-Myers Squibb Company (NYSE: BMY) today announced initial results from the pivotal Phase 3 study, CheckMate -227, evaluating the Opdivo (nivolumab) 3 mg/kg pluslow-dose Yervoy (ipilimumab, 1 mg/kg) combination in first-line advanced non-small cell lung cancer (NSCLC) patients with high tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb). In the study, the combination demonstrated a superior benefit for the co-primary endpoint of progression-free survival (PFS) versus chemotherapy (HR 0.58; 97.5% CI: 0.41 to 0.81; p=0.0002). The PFS benefit was observed regardless of PD-L1 expression levels and in both squamous and non-squamous tumor histology. Additionally, based on an early descriptive analysis, encouraging overall survival was observed with the combination versus chemotherapy in patients with high TMB ≥10 mut/Mb (HR 0.79; 95% CI: 0.56 to 1.10).”
“The anti-PD1 immunotherapy nivolumab (Opdivo) given prior to surgical resection of stage 1-3 non-small cell lung cancer (NSCLC) was safe and resulted in major pathological responses in 45 percent of the patients, according to data from a clinical trial presented at the AACR Annual Meeting 2018, April 14-18.
“A major pathologic response is defined as 10 percent or fewer viable cancer cells detectable in the resected tumor following neoadjuvant treatment.”