Ramucirumab Maintenance Combo Shows Benefit in HER2– Gastric/GEJ Cancer

“[T]he benefit of paclitaxel plus ramucirumab early second-line therapy was supported, irrespective of the clinical and molecular subgroups," according to study authors.

Switch maintenance therapy with paclitaxel plus ramucirumab (Cyramza) significantly improved progression-free survival (PFS) and demonstrated other benefits vs continued chemotherapy in patients with advanced HER2-negative gastric or gastroesophageal junction (GEJ) cancer, according to findings from the phase 3 ARMANI trial (NCT02934464) published in Lancet Oncology.¹

Data showed a median PFS of 6.6 months (95% CI, 5.9-7.8) in the switch maintenance arm vs 3.5 months (95% CI, 2.8-4.2) in the continued oxaliplatin-based chemotherapy arm (HR, 0.61; 95% CI, 0.48-0.79; P = .0002). PFS outcomes typically favored the switch maintenance arm across prespecified subgroup analyses.

Ramucirumab/paclitaxel yielded a median overall survival (OS) of 12.6 months (95% CI, 11.5-15.0) vs 10.4 months (95% CI, 8.0-13.1) with continued chemotherapy (HR, 0.75; 95% CI, 0.58-0.96; P = .025). Additionally, OS improved with the ramucirumab regimen across most key clinical subgroups. The median time to treatment failure was 6.2 months (95% CI, 5.7-7.5) and 3.1 months (95% CI, 2.8-3.9) in the experimental and comparator arms, respectively (P <.0001).

Following random assignment, the objective response rate (ORR) was 19% (95% CI, 12%-28%) in the experimental arm vs 16% (95% CI, 10%-24%) in the control arm (odds ratio [OR], 1.26; 95% CI, 0.60-2.63; P = .58). Any tumor shrinkage occurred among 59% and 38% of patients in each respective arm, and the disease control rate (DCR) was 85% (95% CI, 76%-91%) vs 54% (95% CI, 44%-63%), respectively (OR, 4.94; 95% CI, 2.48-9.84; P <.0001).

“[T]he benefit of paclitaxel plus ramucirumab early second-line therapy was supported, irrespective of the clinical and molecular subgroups,” lead study author Giovanni Randon, MD, from the Medical Oncology Department at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, wrote with coauthors.¹ “The paclitaxel plus ramucirumab switch maintenance treatment regimen might represent a novel postinduction therapy for patients who are not eligible for immune checkpoint inhibitors or targeted agents, and the strategy could be investigated again in future trials with PD-1 or CLDN18.2 inhibitors in biomarker-selected populations.”

Investigators of this open-label, multi-center phase 3 study assessed 280 patients with advanced unresectable or metastatic HER2-negative gastric or GEJ cancer who experienced disease control after 3 months of leucovorin plus fluorouracil and oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (Xeloda; CAPOX). Patients were randomly assigned 1:1 to receive paclitaxel at 80 mg/m² on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days intravenously in the switch maintenance arm (n = 144) or continue FOLFOX or CAPOX for 12 additional weeks followed by fluoropyrimidine maintenance in the control group (n = 136).

The trial’s primary end point was PFS per investigator assessment using RECIST v1.1 criteria. Secondary end points included OS, time to treatment failure, ORR, and safety.

Patients 18 years and older with an ECOG performance status of 0 or 1, a life expectancy of 12 weeks or longer, and radiological evidence of clinical benefit following the last dose of lead-in chemotherapy were eligible for enrollment.² Those with HER2-positive disease, an active prior malignancy within 3 years of study entry, or significant bleeding disorders were ineligible to enroll.

In the switch maintenance and control arms, respectively, most patients were male (67% vs 61%), younger than 70 years (74% vs 68%), and had an ECOG performance status of 0 (75% vs 65%). Additionally, most from each arm had gastric cancer (74% vs 74%), no prior gastrectomy (72% vs 77%), no liver metastases (75% vs 70%), at least 2 metastatic sites (51% vs 57%), and synchronous metastases (78% vs 82%). The most common first-line induction regimen was FOLFOX in each arm (81% vs 87%), and most patients achieved stable disease on frontline treatment (46% vs 43%).

Overall, 58% of patients in the switch maintenance arm and 56% in the control group received any post-discontinuation systemic therapy. The most common subsequent regimen was irinotecan-containing regimens in the switch maintenance group (36%) and paclitaxel/ramucirumab in the control group (46%).

Investigators noted grade 3 or higher treatment-related adverse effects (TRAEs) in 40% of patients who received ramucirumab/paclitaxel and 21% of those who received continued FOLFOX or CAPOX. The most common grade 3/4 toxicities in each arm included neutropenia (26% vs 10%), peripheral neuropathy (6% vs 7%), and arterial hypertension (6% vs 0%). Serious AEs affected 20% and 11% of patients in each arm.

At least 1 dose reduction occurred in 52% of the switch maintenance group and 63% of the control group. There were no treatment discontinuations or deaths associated with TRAEs.

References

1. Randon G, Lonardi S, Fassan M, et al. Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line oxaliplatin-based chemotherapy in patients with advanced HER2-negative gastric or gastrooesophageal junction cancer (ARMANI): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024;25:1539-1550. doi:10.1016/S1470-2045(24)00580-1
2. Assessment of ramucirumab plus paclitaxel as switch MANteInance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers (ARMANI). ClinicalTrials.gov. Updated September 13, 2021. Accessed March 13, 2025. https://tinyurl.com/3dxhn63a