Fengyun male world advanced gastric cancer first-line immunotherapy who and fight?

Gastric cancer is one of the most common malignant tumors in China, not only the base (about 42% of global gastric cancer patients), late stage (higher proportion of patients with advanced diagnosis), poor survival (advanced gastric cancer 5-year survival rate of only 9.4%), and low third-line treatment rate, most patients choose to "abandon" treatment.
recent years, there is growing evidence to support the feasibility of inhibiting the programmed cell death subject-1 (PD-1) and its ligation (PD-L1) in chemotherapy resoccupable GC/GEJC.
Navuliyu monoanti (O) and Pabliju monoanti (K) were initially approved in Japan and the United States for three-line treatment of progressive stomach or gastroesophageal adenocarcinoma (GC/GEJC), respectively.
March 2020, O-drugs were also approved in China for the treatment of advanced GC/GEJC ≥ 2-line systemic therapy.
data are insufficient and controversial, current research is turning to front-line applications or focusing on joint drug use strategies.
Following the KEYNOTE-062 fold, the Checkmate-649 study published at this year's ESMO Conference was both exciting and thought-provoking;
up all over the world, the group out; stomach cancer line, who fights? In today's brilliant immunotherapy, can new progress push the history of first-line treatment of advanced stomach cancer to the next change? In particular, this paper made a retrospective inventory for the reference of the kings.
"OK" double male article one, Paboli Pearl single resistance - across the ridge side into a peak 1. KEYNOTE-062 Study: In keyNOTE-059 study cohort 2, 25 patients with late HER2-negative GC/GEJC received first-line Pabli pearl monoantigen and 5-FU/cisplatin therapy.
ORR was 60%, PD-L1-positive CPS≥1 patients were 69%, and the medium OS was 13.8 months.
The data are exciting, and the researchers designed the first global, randomized, phase III KEYNOTE-062 study using IO monodrative or combination chemotherapy in late-stage HER2-negative GC/GEJC first-line therapy, hoping to take data from K-drug or combination chemotherapy to compare simple chemotherapy.
source: NextMed Database The statistical design of the study was complex, but the results were less than satisfactory.
for patients with CPS≥1, the OS of the K drug was not inferior to chemotherapy, for patients with CPS≥10, the OS of the K drug was better than chemotherapy, and the combination of the K drug was not able to extend the survival further than chemotherapy alone.
Following Keynote-062, there have been a variety of explanations and guesses about negative outcomes, including combination therapy options, screening of molecular markers, regional differences, ethnic differences, statistical design, and differences between different PD-1 monoants.
: At the NextMed Database 2020 ASCO Conference, researchers published the results of the KEYNOTE-062 study of Asian populations.
OS data for the Asian population were better than for the overall population.
in patients with CPS≥1, the meso OS in the K and chemotherapy groups was 22.7 months and 13.8 months (HR=0.54), respectively, and in patients with CPS≥10, the medium OS in the K group was nearly 2 times that of the chemotherapy group, at 28.5 months and 14.8 months (HR=0.43), respectively.
researchers are now further analyzing the factors that affect outcomes in Asian populations to see which patients are most likely to benefit from first-line immunotherapy.
biomarkers, the MSI-H subgroup analysis updated on ESMO in 2019 showed that K-drug monotherapy or combination chemotherapy had significant clinical benefits for patients with MSI-H advanced gastric cancer;
addition, in a small number of patients with late TMB-H (≥10 mut/Mb) GC/GEJC, K-drug monotherapy and K-drug-plus chemotherapy showed potential OS benefits compared to chemotherapy.
source: NextMed Database 2. KEYNOTE-659 Study: Geometry of Efficacy in Japanese Populations? KEYNOTE-659 study is a non-randomized, multi-center, open IIb phase study conducted in Japanese population, which evaluated the effectiveness and safety of K-drug combination chemotherapy as HER2-negative, PD-L1-positive advanced GC/GEJC first-line therapy.
April 2020, the European Journal of Cancer reported preliminary data for the study, K-SOX.
: NextMed Database Queue 1 included 54 assessable patients with a medium follow-up time of 10.1 months.
ORR and DCR assessed by BICR were 72.2% and 96.3%, respectively.
DOR, TTR, PFS, and OS were not reached, 1.5 months, 9.4 months, and not reached, respectively.
57.4% of patients reported treatment-related adverse events (TRAEs) of level 3 and above.
study suggests that for first-line treatments of late GC/GEJC, K-drug combined with S-1 plus Osaliplain showed encouraging efficacy and manageable safety characteristics.
3. HER2-positive GC/GEJC: Targeting immune double-sword combination Given the relatively limited benefits of gastric cancer immunodrive monotherapy, immuno-targeted therapy may be the key to a breakthrough.
May 2020, The Lancet Oncology published a Phase II study online of the first-line treatment of HER2-positive metastatic gastric cancer with K-drug-curto-bead monoantigen-chemotherapy.
: The NextMed database had 37 patients in the group as of August 6, 2019, with a medium follow-up time of 13.0 months.
joint solutions are well-resistant and inspiring, with ORR up to 91% and DCR up to 100%.
PFS was 13 months for patients with no disease progression at 6 months, 80% for 12 months and 27.3 months for the medium OS.
correspondingly, the current first-line standard treatment for such patients is curvature monoanto-anti-combination FP chemotherapy, OS about 13.8 months, ORR about 47%.
these encouraging improvements in efficacy, the Global RandomIzed Double Blind III study KEYNOTE-811 is under way.
4. "Coke Combination": In July 2020, The Lancet Oncology published an open-label, one-arm Phase II study (EPOC1706) online to assess the anti-tumor activity and safety of patients with advance gastric cancer in the first or second-line treatment of K-drug combined with lenphatini.
as of March 20, 2020, a total of 29 patients were included in first- or second-line treatment, with a medium follow-up time of 12.6 months.
20 of the 29 patients (69%, 95% CI 49-85) had objective efficacy, an increase of about 54% compared to single-drug treatment.
, the medium progress-free lifetime was 7.1 months, and the medium total survival rate was not reached (95% CI 11.8 months to not reached).
source: In terms of nextMed database security, the most common level 3 treatment-related adverse events were hypertension (11 cases, or 38%), proteinuria (5 cases, 17%), plateplate reduction (2 cases, 7%).
no level 4 treatment-related adverse events, severe treatment-related adverse events or treatment-related deaths occurred.
In addition, the KEYNOTE-859 and KEYNOTE-811 studies explored Pembrolizumab-chemotherapy-comparison placebo-chemotherapy first-line treatment of HER2-negative advanced stomach cancer, K-drug-curto-bead monoanti-chemotherapy-virulent single-dose-chemotherapy first-line treatment of HER2-positive advanced gastric cancer, both of which were included in the group.
2nd, Navuliyu single resistance - willow dark flowers and another village 1. CheckMate-649 Study: The new standard for gastric cancer, following keyNOTE-062, was published this year in ESMO's CheckMate-649 study, which validated the effects of O-drug combination chemotherapy in prolonging PFS and OS in patients with PD-L1 CPS≥5, and also saw statistical differences in CPS≥1 and the population as a whole.
It is worth mentioning that CheckMate-649 is based on the first part of the Attarction-4 study, the Checkmate-032 study and the adjustment of the PD-L1 CPS≥5 population, and the study program has been adjusted several times to reach the largest sample size in clinical studies of prehistoric advanced gastric cancer.
source: NextMed database Specifically, in the PD-L1 CPS≥5 population, The OS of Navuliyu mono-anti-combination chemotherapy compared to chemotherapy alone was 14.4 vs 11.1 months (HR=0.71).
OS also had significant statistical differences in the PD-L1 CPS≥1 (14.0 vs 11.3 months, HR=0.77) and the overall population (13.8 vs 11.6 months, HR=0.80) subgroups.
, in the general population (7.7 vs 6.9 months, HR=0.77), PD-L1 CPS≥1 (7.5 vs 6.9 months, HR=0 .74) and PD-L1 CPS≥5 (7.7 vs 6.0 months, HR-0.68) population, PFS of Navuliyu monoantigen combination chemotherapy also reached the preset endpoint.
in the subgroup of PD-L1 CPS≥5, the combined immunotherapy group had ORR of 60%, compared with 45% in the chemotherapy-simple group and 9.5 months and 7.0 months in both groups.
safety, the rates of adverse reactions at any level in the combined chemotherapy group and the pure chemotherapy group were 94% and 89%, respectively, and the rates of adverse reactions at levels 3 to 4 were 59% and 45%, respectively.
2. ATTRACTION-04 Study: The attraction-4 study on the first line of gastric cancer in Asia, conducted in Japan, South Korea and Taiwan, China, also verified the role of Navuliyu monoanti-combination chemotherapy in prolonging PFS, reaching one of its main research endpoints.
source: NextMed database results show that PFS for Navuliyu monoantigen combination chemotherapy is significantly better than chemotherapy (medium PFS: 10.5vs. 8.3 months, HR=0.68), but the OS is similar (MesoOS: 17.5 vs.17.2 months, HR=0.90).
orR was significantly higher in the chemotherapy group (57.5% vs. 47.8% ;P 0.0088).
safety, the risk of adverse reactions was higher in the 3-5 levels of the Navuliyu monoantigen combination group than in the chemotherapy group (57.9% vs 49.2%).
it's worth noting that Attraction-4 is a population-wide study that doesn't have molecular marker selection.
the results of three Phase III clinical studies on the combination of first-line chemotherapy and PD-1 monotherapy for advanced stomach cancer have published results, but the results are not the same, and the possible causes are still foggy.
optimize the combined and sequential sequence of immunotherapy to achieve optimal results? How do I select the appropriate biomarkers among MSI-H, PD-L1 high expression, high TMB, and EBV positives? How to change the tumor micro-environment and overcome drug resistance? Further exploration is still needed.
: Checkmate-649, Attraction-4 and Keynote-062 research data (non-head-to-head comparison) are at the end of qingping, and waves are in the air.
Although there are K medicine, O drug gold jade in front, domestic PD-1 "F4" is not willing to lag behind, in the last two years Karelli single resistance, Xindili single resistance, Terriple single resistance, for Reilly pearl single resistance in the field of stomach cancer sustained force, anti-PD-L1 Shugli monoanti also among the columns, the late first-line exploratory research has been published, each has a thousand autumn;
1. After 4 to 6 cycles of a Karelliju single anti-combination chemotherapy sequence joint TKI: DCR up to 78.3% Peking University Oncology Hospital, Professor Shen Lin led a Carelliju single anti-combination CAPOX program, the effectiveness of the first-line treatment of HER2-negative or metastatic GC/GEJC by Karelliju single-line anti-combination apatini was conducted, and the effectiveness of immunogenic joint anti-vascular drugs and chemotherapy for advanced gastric front-line cancer treatment was initially validated.
results of Phase II, previously published by ASCO in 2019, showed that 43 of the 48 patients in the group were assessable; PR (44%), disease stabilization (SD) in 14 patients, disease progression (PD) in 10 patients, objective remission rate (ORR) of 58.7%, disease control rate (DCR) of 87.3%.
based on this result, the team launched a Phase III clinical study at the National Multi-Center in March 2019.
2. The DCR of Sindili monoanti-anti-combination chemotherapy is up to 100%, and the ORIENT-106 study is worth looking forward to in ASCO 2019, which published a phase IB study (queue F) for the first-line treatment of HER2-negative localized late stage or metastasis GC/GEJC (queue F).
in August 2020, the study was officially published at BMCCancer.
source: NextMed database as of May 1, 2019, with a medium follow-up time of 7.8 months.
orR was 85.0% for 20 patients and 100.0% for DCR. <br/