LBA4 - Switch maintenance with ramucirumab plus paclitaxel versus continuation of oxaliplatin-based chemotherapy in advanced HER2-negative gastric or gastroesophageal junction (GEJ) cancer: Final results and key biomarkers of the ARMANI phase III trial

Background

In patients (pts) with HER2-negative advanced gastric or GEJ cancer and PD-L1 low/absent expression switch consolidation maintenance or early second-line therapy may prolong the benefit of the initial strategy and delay clinical deterioration.

Methods

Pts with HER2-negative advanced gastric/GEJ cancer without disease progression after 3 months (mos) of initial oxaliplatin-based chemotherapy were randomized 1:1 to ramucirumab plus paclitaxel (arm A) vs CAPOX/FOLFOX for additional 3 months followed by fluoropyrimidine monotherapy maintenance (arm B). The primary endpoint was PFS. A sample size of 280 pts achieved a 90% power to detect as significant at a 5% level (2-sided log-rank test) a median PFS increase from 4 to 6 mos (target HR=0.67). As exploratory biomarkers, PD-L1 CPS, Claudin 18 (CLDN18) and mismatch repair (MMR) status were assessed by IHC.

Results

At a median follow-up of 43.7 months (IQR: 24.0 – 57.9), median PFS was 6.6 vs. 3.5 mos in Arm A vs. B (HR=0.63, 95%CI 0.49-0.81; P<0.001). 24-mos RMST analysis showed a statistically significant 2.4-mos average increment (P=0.002). Median OS was 12.6 vs. 10.4 mos in Arm A vs. B (HR=0.75, 95%CI 0.58-0.97; P=0.030). PFS and OS favoured switch maintenance across all clinical subgroups. 179 (64%), 189 (67%) and 214 (76%) were evaluable for CLDN18, PD-L1 CPS and MMR/MSI status. Positive CLDN18 expression was found in 63 (35%), PD-L1 CPS≥ 5 and ≥10 in 76 (40%) and 57 (29%) pts, whereas deficient MMR and/or MSI-high in 14 (6%). There was no significant interaction between CLDN18 status, PD-L1 CPS <5 and treatment arms in terms of both PFS/OS. Collectively 58 (35%) of the biomarker-assessable pts had both CLDN18 negative and PD-L1 CPS<5. In this subgroup median PFS was 7.5 vs. 4.2 mos in Arm A vs. B (HR 0.69, 95%CI 0.41-1.18; P=0.179).

Conclusions

Paclitaxel and ramucirumab switch maintenance consistently prolongs survival irrespective of the investigated clinical and molecular subgroups.

Clinical trial identification

NCT02934464.

Legal entity responsible for the study

The authors.

Funding

Eli Lilly and Company.

Disclosure

S. Tamberi: Financial Interests, Personal, Advisory Board: Gilead, AstraZeneca. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, MSD, Bayer, Astellas, Takeda, GSK, Johnson&Johnson, Rottapharm; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, BMS, Lilly, Servier, Bayer, Pierre Fabre, AstraZeneca, Astellas, Daiichi Sankyo, Takeda; Financial Interests, Personal, Expert Testimony: Ipsen; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus; Financial Interests, Institutional, Invited Speaker: Lilly, Amgen. All other authors have declared no conflicts of interest.