The recent ONO-4538-12 clinical study released at the ASCO-GI conference showed that compared with placebo, Nivolumab reduced the risk of death of patients by 37%, and the overall 12-month survival rate of patients treated with Nivolumab reached 26.6%. The 12-month overall survival rate of placebo-administered patients was only 10.9%.
On January 19, 2017, Bristol-Myers Squibb announced the results of a clinical study called ONO-4538-12, which showed that Nivolumab significantly reduced the risk of death in patients with advanced gastric cancer who were ineffective or intolerant to standard treatment 37% (HR0.63; p <0.0001), and there is currently no standard treatment for such patients. The ONO-4538-12 study is a phase III randomized, double-blind, placebo-controlled clinical study evaluating the efficacy and safety of Nivolumab in such patients. The primary endpoint of the study was overall survival (OS). The median OS in the Nivolumab group and the placebo group were 5.32 months (95% CI: 4.63-6.41) and 4.14 months (95% CI: 3.42-4.86) (p <0.0001). The 12-month overall survival rates of the Nivolumab group and the placebo group were 26.6% (95% CI: 21.1-32.4) and 10.9% (95% CI: 6.2-17.0), respectively. After the patient was treated with Nivolumab, the secondary endpoint objective response rate reached 11.2% (95% CI: 7.7-15.6), and the median duration of response was 9.53 months (95% CI: 6.14-9.82). The objective response rate in the placebo group was 0% (95% CI: 0.0-2.8).
Nivolumab’s safety is consistent with previous reports of solid tumor studies. In the Nivolumab group and placebo group, the incidence of all treatment-related adverse events (TRAE) was 42.7% and 26.7%, and the incidence of grade 3/4 TRAE was 10.3% and 4.3%, respectively. Grade 3/4 TRAEs occurred in more than 2% of patients in the Nivolumab group including diarrhea, fatigue, decreased appetite, fever, and increased AST and ALT. Grade 3/4 TRAEs occurred in more than 2% of patients in the placebo group were fatigue and decreased appetite . In the Nivolumab group and the placebo group, the incidence of discontinuation TRAE was similar, 2.7% and 2.5%, respectively.
ONO-4538-12-onderzoeksgegevens werden aangekondigd in het baanbrekende mondelinge rapport van het 2017 Gastrointestinal Oncology Symposium (ASCOGI) in San Francisco, Californië, VS, van 2:00 tot 3:30 uur op 19 januari (uittreksel nr. 2).
The ONO-4538-12 study is the first phase III randomized clinical trial of tumor immunotherapie that improves the survival rate of patients with advanced or relapsed gastric cancer . We think the results of Nivolumab treatment are encouraging because gastric cancer is the cause of cancer deaths worldwide At the forefront of this, there is a huge unmet need in patients with advanced gastric cancer who are intolerant to chemotherapy or who have failed chemotherapy, “said Ian M. Waxman, MD, head of research and development at Bristol-Myers Squibb Gastrointestinal Cancer.
"Deze resultaten bevestigen het klinische voordeel van nivolumab bij de behandeling van vergevorderde of recidiverende maagkanker, en bieden een sterke basis voor verder onderzoek naar nivolumab voor de behandeling van maagkanker", aldus Yoon-KooKang, MD en MD van het Medical College of Oncology, de belangrijkste klinische onderzoeker van het Seoul Asian Medical Center, Ulsan University, Zuid-Korea.
Over ONO-4538-12 onderzoek
The ONO-4538-12 study (NCT02267343) is a phase III, randomized, double-blind, placebo-controlled clinical study conducted in Japan, South Korea, and Taiwan. It evaluated the unresectability (cannot be removed by surgery) and standard of Nivolumab Therapeutic treatment is ineffective or intolerant in the treatment of patients with advanced or recurrent gastric cancer (including gastroesophageal junction cancer) in patients with efficacy and safety. The clinical study was conducted by Japan’s Ono Pharmaceutical Co., Ltd., a Bristol-Myers Squibb Nivolumab R & D partner .
In de ONO-4538-12-studie kregen patiënten eenmaal per twee weken nivolumab 3 mg / kg of placebo totdat de tumor vorderde of stopte vanwege ondraaglijke toxiciteit. Het primaire eindpunt OS werd beoordeeld op effectiviteit ten opzichte van placebo. Secundaire eindpunten waren objectief responspercentage, responsduur, progressievrije overleving, optimaal totaal responspercentage, tijd tot tumorrespons, ziektecontrolepercentage en veiligheidsgerelateerde variabelen.
NIVOLUMAB-indicatie goedgekeurd door de Amerikaanse Food and Drug Administration (FDA)
Nivolumab monotherapy can be used to treat BRAFV600 mutation-positive unresectable or metastatic melanoma . Based on the significant effect of Nivolumab on progression-free survival, the indication was quickly approved. According to the clinical benefit results of the confirmatory test, the continued approval of the indication can be judged.
Nivolumab-monotherapie kan worden gebruikt om BRAFV600 wildtype inoperabel of gemetastaseerd melanoom te behandelen.
Nivolumab in combinatie met Ipilimumab is geschikt voor de behandeling van patiënten met een inoperabel of gemetastaseerd melanoom. Op basis van het opmerkelijke effect van de therapie op de progressievrije overleving werd de indicatie snel goedgekeurd. De blijvende goedkeuring van de indicatie zal worden beoordeeld op basis van de resultaten van de klinische voordelen van de bevestigende test.
Nivolumab can be used to treat metastatic niet-kleincellige longkanker (NSCLC) that progresses during or after platinum-based chemotherapy regimens. For patients with EGFR mutations or ALK rearrangements, before using Nivolumab, it should be confirmed that the patients have used FDA-approved therapeutic drugs for these genetic abnormalities and disease progression has occurred.
Nivolumab kan worden gebruikt voor de behandeling van patiënten met gevorderd niercelcarcinoom (RCC) die anti-angiogene geneesmiddelen hebben gebruikt.
Nivolumab can be used for autologous hematopoietic stem cell transplantation (HSCT) and after transplantation, brentuximabvedotin is used to treat recurrent or progressive classic Hodgkin-lymfoom (cHL). Based on the drug’s significant effect on the overall response rate, the indication was approved quickly. The continued approval of the indication will be judged based on the clinical benefit results of the confirmatory test.
