Paclitaxel and ramucirumab switch maintenance therapy prolongs survival in HER2-negative advanced GEJ cancer
Dr Giovanni Randon - The National Cancer Institute of Milan, Milano, Italy
The ARMANI trial is a phase III trial conducted in the first-line setting of the advanced HER2-negative disease. The ARMANI trial enrolled patients with advanced HER2-negative gastric cancer who had disease control after an induction phase of three months of FOLFOX or CAPOX within the clinical practice and then were randomised on a 1:1 basis to paclitaxel plus ramucirumab, that was the experimental arm, or the control arm which was the continuation of oxaliplatin-based chemotherapy for additional treatments followed by fluoropyrimidine maintenance.
The primary endpoint of this trial was progression free survival. Overall survival was a key secondary endpoint. At ESMO GI 2024 we also presented data regarding PD-L1, CPS, Claudin18.2 and mismatch repair, and their correlation with outcomes.
What was the study design and results?
The ARMANI trial enrolled 280 patients across 31 Italian centres. The median follow-up of the trial was 43.7 months. As I previously said, the primary endpoint was progression free survival, and progression free survival was significantly improved by the switch maintenance strategy with paclitaxel plus ramucirumab. In fact, median progression free survival was 6.6 versus 3.5 months. This corresponded to a hazard ratio of 0.64 in favour of the experimental arm. Importantly, also the overall survival was significantly improved by the switch maintenance. In fact, the median overall survival was 12.6 versus 10.4 months. This corresponded with a hazard ratio of 0.75 in favour of paclitaxel plus ramucirumab.
In this ESMO presentation we also assessed the impact of the experimental treatment across the key clinical and molecular subgroups. Specifically, the experimental arm with paclitaxel plus ramucirumab significantly improved both PFS and OS across all the key relevant clinical subgroups. Moreover, at ESMO 2024, we presented data regarding key biomarkers, including PD-L1, CPS, Claudin18.2 and mismatch repair, because the assessment of these biomarkers is very important in the patient decision-making in the first-line setting of the advanced HER2-negative disease.
We found that about 41% in the biomarker-evaluable population had PD-L1 CPS of five or more, 39% of patients had Claudin18.2 positivity, and 5% of patients had mismatch repair deficiency, as expected in this patient population. We found no significant interaction between PD-L1 status and the treatment arm, and similar results were observed for the Claudin18.2 status and the treatment arm.
What is the clinical significance of these results?
As you know, advanced HER2-negative gastric cancer is a very hard-to-treat disease, and less than 50% of patients are eligible to second-line therapy due to worsening of performance status following disease progression to up-front chemotherapy regimens. The ARMANI strategy demonstrated that a switch maintenance or an early second-line strategy would improve the patient outcomes irrespective of the main clinical characteristics. Moreover, we also demonstrated that about one out of three patients enrolled in the ARMANI trial had a so-called triple-negative tumour, a triple-negative tumour corresponding to low or absent PD-L1 expression, Claudin18.2 negativity or mismatch repair proficiency. This subset of patients is not eligible to PD-L1 or Claudin18.2 inhibitors, so the ARMANI strategy could represent a promising treatment for patients who are not eligible for targeted therapies.
