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.
Podaci istraživanja ONO-4538-12 objavljeni su u probojnom usmenom izvješću Simpozija za gastrointestinalni onkološki sustav 2017. (ASCOGI) u San Franciscu, u Kaliforniji, SAD, od 2. do 00 sati 3. siječnja (Sažetak br. 30).
The ONO-4538-12 study is the first phase III randomized clinical trial of tumor imunoterapija 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.
"Ovi rezultati potvrđuju kliničku korist Nivolumaba u liječenju uznapredovalog ili rekurentnog karcinoma želuca i pružaju snažnu osnovu za daljnja istraživanja Nivolumaba za liječenje raka želuca", glavni klinički istraživač, Seulski azijski medicinski centar, Sveučilište Ulsan, Jug Komentirao je Korea Yoon-KooKang, dr. Med. I dr. Medicinskog fakulteta za onkologiju.
O istraživanju ONO-4538-12
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 .
U studiji ONO-4538-12, pacijenti su primali nivolumab 3 mg / kg ili placebo jednom u dva tjedna dok tumor nije napredovao ili prestao zbog nepodnošljive toksičnosti. Primarni OS krajnje točke procijenjen je na učinkovitost u odnosu na placebo. Sekundarne krajnje točke uključivale su objektivnu stopu odgovora, trajanje odgovora, preživljenje bez progresije bolesti, optimalnu ukupnu stopu odgovora, vrijeme do odgovora na tumor, stopu kontrole bolesti i varijable povezane sa sigurnošću.
Indikaciju NIVOLUMAB odobrila američka Uprava za hranu i lijekove (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.
Monoterapija Nivolumabom može se koristiti za liječenje BRAFV600 divljeg tipa neopozivog ili metastatskog melanoma.
Nivolumab u kombinaciji s Ipilimumabom pogodan je za liječenje bolesnika s neresektabilnim ili metastatskim melanomom. Na temelju izvanrednog učinka terapije na preživljenje bez napredovanja, indikacija je brzo odobrena. Dalje odobrenje indikacije procijenit će se na temelju rezultata kliničke koristi potvrdnog testa.
Nivolumab can be used to treat metastatic karcinom pluća nedrobnih stanica (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 se može koristiti za liječenje bolesnika s uznapredovalim karcinomom bubrežnih stanica (RCC) koji su koristili antiangiogene lijekove.
Nivolumab can be used for autologous hematopoietic stem cell transplantation (HSCT) and after transplantation, brentuximabvedotin is used to treat recurrent or progressive classic Hodgkinov limfom (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.
