A combination therapy of Cyramza (ramucirumab) and Tagrisso (osimertinib) has demonstrated a significant improvement in progression-free survival (PFS) for patients with TKI-naïve EGFR-mutant non-small cell lung cancer (NSCLC), according to the phase 2 RAMOSE trial. The study, published in the Journal of Clinical Oncology, reveals that the combination therapy extended median PFS to 24.8 months compared to 15.6 months with Tagrisso alone, marking a notable advancement in the treatment of this specific NSCLC subset.
The RAMOSE trial, a US-only, multicenter, open-label, randomized phase 2 study, enrolled 139 patients with NSCLC harboring classical EGFR mutations who had not previously received EGFR tyrosine kinase inhibitors (TKIs). Patients were randomized to receive either Cyramza in combination with Tagrisso (n=93) or Tagrisso alone (n=46). At baseline, 46% of patients had stable central nervous system (CNS) metastases, with 43% in the combination group and 52% in the Tagrisso group.
Progression-Free Survival Outcomes
The primary endpoint of the RAMOSE trial was PFS. Results indicated a significant prolongation of PFS with the combination therapy. Among the 139 patients, 57 PFS events occurred: 32 in the combination group and 25 in the Tagrisso group. Median PFS was 24.8 months in the Cyramza-Tagrisso arm and 15.6 months in the Tagrisso-alone arm.
Notably, the PFS benefit of the Cyramza plus Tagrisso combination was observed across various subgroups, including those defined by age, sex, race, EGFR mutation type (exon 19 deletion or L858R), and the presence of CNS metastases at baseline. In patients with exon 19 deletion, median PFS was 20.5 months in the combination group and 14.1 months in the Tagrisso group. For those with the L858R mutation, median PFS was 24.8 months and 18.4 months in the respective treatment groups.
For the 64 patients with CNS metastases at the start of the study, median PFS was 17.9 months with the combination and 13.8 months with Tagrisso alone. In patients without CNS metastases at baseline, the median PFS was not reached in the combination group and was 18.4 months in the Tagrisso-alone group.
Safety and Tolerability
The combination of Cyramza and Tagrisso was generally well-tolerated, with a safety profile consistent with the known profiles of the individual agents. No grade 5 (fatal) adverse events were reported. One patient in the combination group experienced a grade 4 (life-threatening) event of hyponatremia, which was not considered treatment-related.
The most common grade 3 (severe) adverse events in the combination group were diarrhea, fatigue, headache, and cough. In the Tagrisso-alone group, common grade 3 events were diarrhea, fatigue, and rash. Grade 3 side effects occurred in 53% of patients in the combination group and 41% in the Tagrisso-alone group.
Treatment discontinuations due to treatment-related adverse events were similar between the two groups: 9.7% in the combination group and 8.7% in the Tagrisso-alone group. Among patients receiving Cyramza, 56 experienced at least one dose interruption, commonly due to proteinuria, hypertension, infusion reactions, anemia, or thrombocytopenia.
"There were no major bleeding or clotting events in the RAMOSE trial, and there was no new safety signal," the researchers stated. "Overall, patients were highly compliant with 86.6% dose intensity, also indicating excellent safety and tolerability."
