OS benefit in ARMANI, but is it worth it?

Modest improvements in progression-free survival (PFS) and overall survival (OS) were reported for patients with HER2-negative advanced gastric or gastroesophageal junction (G/GEJ) cancer and low/absent PD-L1 expression who switched their consolidation maintenance or early second-line therapy from CAPOX/FOLFOX to ramucirumab plus paclitaxel. However, toxicities were higher, and if patients would progress they would enter third-line therapy.

The past year has seen 5 new approvals for G/GEJ cancer treatments, all biomarker-driven, leaving patients without these markers in need of alternative strategies. About 40% of patients with locally advanced or metastatic G/GEJ cancer never reach second-line therapy, making the initial treatment phase critical. Dr Giovanni Randon (Fondazione IRCCS Istituto Nazionale dei Tumori, Italy) presented a potential strategy for patients with HER2-negative advanced G/GEJ cancer from the randomised, open-label, multicentre phase 3 ARMANI trial (NCT02934464) [1].

ARMANI randomised 280 patients who showed no disease progression after 3 months of initial oxaliplatin-based chemotherapy to receive either ramucirumab plus paclitaxel (8 mg/kg on days 1 and 15) plus paclitaxel (80 mg/m² on days 1, 8, 15, and every 28 days thereafter) (Arm A) or to continue with CAPOX/FOLFOX for another 3 months, followed by fluoropyrimidine monotherapy maintenance (Arm B). The primary endpoint was PFS difference between the 2 arms [2].

The median PFS was 6.6 months in Arm A compared with 3.5 months in Arm B (HR 0.63; 95% CI 0.49–0.81; P<0.001). Median OS was 12.6 months in Arm A versus 10.4 months in Arm B (HR 0.75; 95% CI 0.58–0.97; P=0.030). However, grade 3 or higher neuropathy and other toxicities were more common in Arm A.

An exploratory biomarker analysis showed no significant interaction between CLDN18 status, PD-L1 combined positive score (CPS) <5, and treatment outcomes. Positive CLDN18 expression was found in 35% of the participants, and 40% had PD-L1 CPS ≥5. In the subgroup with CLDN18-negative status and PD-L1 CPS <5 (34% of the participants), the median PFS was 7.5 versus 4.2 months in Arm A and B, respectively (HR 0.69; 95% CI 0.41–1.18; P=0.179).

These findings suggest that switching to ramucirumab and paclitaxel maintenance may prolong survival across various clinical and molecular subgroups. However, the increased toxicities, patients’ quality-of-life, and the implication of already having used 2 lines of therapy if patients progress must be considered when deciding on this treatment approach.

1. Randon G, et al. 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 3 trial. Abstract LBA4, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.
2. Di Bartolomeo M, et al. BMC Cancer. 2019;19(1):283.

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Posted on 21 August 202421 August 2024