This is another option for gastric cancer that is showing efficacy in non-HER-2 neutrophils, as Enhertu showed superiority in a recent study in the second line over taxol and cyramza (destiny gastric 4).
Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS).
A double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL).
INTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P = .001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P = .006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P < .0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P = .0043). The toxicity profile was consistent with that of previous reports.
Regorafenib improves survival compared with placebo in refractory AGOC.
Preoperative chemoradiation added to perioperative chemotherapy (ECF/ECX or FLOT) was not beneficial. Of note this study was done in a non-US, predominantly caucasian population. It seems XRT has less and less of a role in gastroesophageal junction / gastroesophageal (GEJ/GE) cancers.
Fruquintinib was recently approved for colorectal cancer, advanced refractory stage. It is an oral VEGF inihibitor, now in combination with taxol, showing improved progression-free survival (PFS) and trends to improve overall survival (OS), another option for those patients for second line therapy. This PFS benefit was close to benefit of adding ramucirimab to taxol. This combination showed OS benefit, too. So, it is not surprising that adding VEGF to taxol showed superiority to taxol alone in those patients. In both trials, immunotherapy was not used in the first line setting.
This is a study showing tumor agnostic activity of trastuzumab deruxtecan (T-DXd) with an all-comer overall response rate (ORR) of 37.1%, duration of response (DOR) of 11.3 months and an overall survival (OS) of 13.4 months in an otherwise heavily pre-treated group. Those with IHC-3+ derived larger benefit than 2+. Patients with ERBB2 mutations who had no expression of HER2 were excluded from the trial.
Interesting correlation between H. Pylori infection and increased risk of gastric cancer in patients with pathogenic homologous-recombination mutations. The risk was additive and not multiplicative as many had thought.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
