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 nádor 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.
Údaje o výskume ONO-4538-12 boli oznámené v prelomovej ústnej správe z roku 2017 Gastrointestinálne onkologické sympózium (ASCOGI) v San Franciscu v Kalifornii v USA, ktoré sa konalo 2. januára od 00:3 do 30:19 (abstrakt č. 2).
The ONO-4538-12 study is the first phase III randomized clinical trial of tumor imunoterapia 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.
„Tieto výsledky potvrdzujú klinický prínos Nivolumabu pri liečbe pokročilého alebo opakovaného karcinómu žalúdka a poskytujú silný základ pre ďalší výskum Nivolumabu pri liečbe karcinómu žalúdka,“ hlavný klinický výskumník, Soulské ázijské lekárske centrum, Univerzita Ulsan, Juh Korea Yoon-KooKang, MD a MD z Medical College of Oncology, sa vyjadrili.
Informácie o výskume 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 .
V štúdii ONO-4538-12 dostávali pacienti nivolumab v dávke 3 mg / kg alebo placebo raz za dva týždne, kým nedošlo k progresii alebo prerušeniu nádoru z dôvodu netolerovateľnej toxicity. Účinnosť primárneho cieľového ukazovateľa OS sa hodnotila v porovnaní s placebom. Sekundárne cieľové ukazovatele zahŕňali mieru objektívnej odpovede, trvanie odpovede, prežitie bez progresie, optimálnu celkovú mieru odpovede, čas do odpovede nádoru, mieru kontroly ochorenia a premenné súvisiace s bezpečnosťou.
Indikácia NIVOLUMAB schválená americkým úradom pre kontrolu potravín a liečiv (FDA)
Nivolumab monotherapy can be used to treat BRAFV600 mutation-positive unresectable or metastatic melanóm . 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.
Monoterapia nivolumabom sa môže použiť na liečbu neresekovateľného alebo metastatického melanómu divokého typu BRAFV600.
Nivolumab v kombinácii s ipilimumabom je vhodný na liečbu pacientov s neresekovateľným alebo metastatickým melanómom. Na základe pozoruhodného účinku terapie na prežitie bez progresie ochorenia bola indikácia rýchlo schválená. Priebežné schválenie indikácie sa posúdi na základe výsledkov klinického prínosu potvrdzovacieho testu.
Nivolumab can be used to treat metastatic nemalobunkový karcinóm pľúc (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 sa môže použiť na liečbu pacientov s pokročilým renálnym bunkovým karcinómom (RCC), ktorí užívali antiangiogénne lieky.
Nivolumab can be used for autologous hematopoietic stem cell transplantation (HSCT) and after transplantation, brentuximabvedotin is used to treat recurrent or progressive classic Hodgkinov lymfóm (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.
