Rivoceranib Improves PFS, but Misses on OS in Gastric/GEJ Cancer
Rivoceranib did not produce a statistically significant improvement in overall survival vs placebo, according to findings from the phase 3 ANGEL trial in gastric or gastroesophageal junction cancer.
3D Illustration of esophageal cancer in the human male: © Lars Neumann - stock.adobe.com
April is Esophageal Cancer Awareness Month. This month, Targeted Oncology is highlighting research in the field of esophageal cancer treatment.
While rivoceranib (apatinib) delivered improvements in progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) compared with placebo in patients with gastric or gastroesophageal junction (GEJ) cancer, the agent did not improve overall survival (OS), missing the primary end point of the phase 3 ANGEL trial (NCT03042611).1
The OS with rivoceranib was 5.78 months vs 5.13 months with placebo (HR, 0.93; 95% CI, 0.74-1.15; P =.4724), which was not a statistically significant improvement. PFS as assessed by blinded independent central review was 3.52 months with rivoceranib vs 1.77 months with placebo (HR, 0.58; 95% CI, 0.47-0.71, P <.0001). The ORR was 6.5% with rivoceranib vs 1.3% with placebo (P =.0119), and DCR was 40.3% with rivoceranib vs 13.2% with placebo (P <.0001).
“Ultimately, the ANGEL study did not demonstrate a statistically significant improvement in the primary endpoint, OS in the [intent-to-treat] population,” study authors wrote. However, the authors added that, “While improvement of OS remains the gold standard for oncology studies and the ultimate goal for new therapies, it remains an endpoint that can be easily confounded or diluted, principally by poststudy anticancer therapies.”
Notably, a greater OS improvement was observed among patients who had received at least 4 prior lines of therapy, with 6.34 months with rivoceranib vs 4.73 months with placebo (P =.0192). PFS in this subgroup was 3.52 months with rivoceranib vs 1.71 months with placebo (P <.0001).
“The OS benefit observed in patients receiving rivoceranib in the ≥4th line warrants further study in a dedicated trial of this subgroup,” study authors wrote.
A total of 460 patients were randomized in the study between March 2017 and October 2018 across 95 sites in 12 countries. Most (76.7%) patients were male, and the median age was 60. The median durations of treatment were 1.91 months and 1.78 months in the rivoceranib and placebo arms, respectively.
Regarding safety, 99.7% of patients in the rivoceranib arm and 95.4% of patients in the placebo arm experienced an adverse event (AE) of any grade. In the rivoceranib arm, 47.6% of patients experienced a serious AE, and 6.8% of patients died due to an AE. In the placebo arm, 43.7% of patients experienced a serious AE, while 7.3% of patients died due to an AE. Treatment-related AEs of any grade were observed in 86.8% of patients in the rivoceranib arm and 57.0% patients in the placebo arm.
The most common treatment-emergent AEs in the rivoceranib arm were decreased appetite (42.3%), hypertension (34.2%), proteinuria (29.3%), and diarrhea (29.3%). For grade 3 or higher AEs, the most common were hypertension (17.9%), anemia (10.4%), increased aspartate aminotransferase (9.4%), asthenia (8.5%), and proteinuria (7.5%).
