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 svulst 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 forskningsdata ble annonsert i den muntlige banebrytende rapporten fra 2017 Gastrointestinal Oncology Symposium (ASCOGI) i San Francisco, California, USA, fra 2:00 til 3:30 19. januar (Abstract nr. 2).
The ONO-4538-12 study is the first phase III randomized clinical trial of tumor immunterapi 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.
"Disse resultatene bekrefter den kliniske fordelen med Nivolumab i behandlingen av avansert eller tilbakevendende magekreft, og gir et sterkt grunnlag for videre forskning av Nivolumab for behandling av magekreft," sjefsklinikken ved Seoul Asian Medical Center, Ulsan University, Sør Korea Yoon-KooKang, MD og MD ved Medical College of Oncology, kommenterte.
Om ONO-4538-12 forskning
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 .
I ONO-4538-12-studien fikk pasientene nivolumab 3 mg/kg eller placebo en gang annenhver uke inntil svulsten progredierte eller avbrøt på grunn av utålelig toksisitet. Det primære endepunktet OS ble evaluert for effektivitet i forhold til placebo. Sekundære endepunkter inkluderte objektiv responsrate, varighet av respons, progresjonsfri overlevelse, optimal total responsrate, tid til tumorrespons, sykdomskontrollrate og sikkerhetsrelaterte variabler.
NIVOLUMAB-indikasjon godkjent av US Food and Drug Administration (FDA)
Nivolumab monotherapy can be used to treat BRAFV600 mutation-positive unresectable or metastatic melanom . 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 monoterapi kan brukes til å behandle BRAFV600 villtype inoperabelt eller metastatisk melanom.
Nivolumab kombinert med Ipilimumab er egnet for behandling av pasienter med inoperabelt eller metastatisk melanom. Basert på den bemerkelsesverdige effekten av terapien på progresjonsfri overlevelse, ble indikasjonen raskt godkjent. Fortsatt godkjenning av indikasjonen vil bli bedømt basert på de kliniske fordelene fra bekreftelsestesten.
Nivolumab can be used to treat metastatic ikke-småcellet lungekreft (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 brukes til å behandle pasienter med avansert nyrecellekarsinom (RCC) som har brukt anti-angiogene legemidler.
Nivolumab can be used for autologous hematopoietic stem cell transplantation (HSCT) and after transplantation, brentuximabvedotin is used to treat recurrent or progressive classic Hodgkin lymfom (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.
