Patients with EGFR-mutant non-small cell lung cancer who are TKI-naïve benefited from receiving the Cyramza-Tagrisso combination versus Tagrisso alone.
Adding Cyramza (ramucirumab) to Tagrisso (osimertinib) significantly lengthened progression-free survival (PFS) in patients with TKI-naïve EGFR-mutant non-small cell lung cancer (NSCLC) compared with Tagrisso alone.
The phase 2 RAMOSE trial, the findings of which were published in the Journal of Clinical Oncology, evaluated 139 patients. There were 93 patients included in the Cyramza-Tagrisso combination group and 46 patients in the Tagrisso alone group.
At the start of the study, 46% of the patients were reported to have stable central nervous system (CNS) metastases, with 43% in the combination group and 52% in the Tagrisso group.
“The RAMOSE trial is a US-only, multicenter, phase 2 study, which enrolled patients with NSCLC with EGFR classical mutations naïve to EGFR TKIs,” the researchers wrote in the study. “The RAMOSE trial interim analysis showed that the addition of [Cyramza] to [Tagrisso] significantly prolonged PFS to 24.8 months compared with [Tagrisso alone] at 15.6 months.”
TKI-naïve: patients who have not received a tyrosine kinase inhibitor, a targeted cancer therapy.
Progression-free survival (PFS): time patients live with cancer without it worsening or spreading.
Metastases: the spread of cancer into other areas of the body.
Primary end point: the main goal of the study that is measured at the end.
Hyponatremia: lower levels of sodium in the blood than normal.
Dose interruption: skipping doses of treatment.
Among the 139 patients included in the study, 57 PFS events occurred, the researchers reported. Specifically, these included 32 PFS events in the combination group and 25 in the Tagrisso group.
The primary end point of the study was PFS, according to the study. The median PFS in the combination and Tagrisso alone groups were 24.8 months and 15.6. months, respectively.
Of note, the PFS benefits of the Cyramza plus Tagrisso combination were observed in most of the study’s major subgroups, researchers wrote. This was regardless of patient age, sex, race, EGFR mutation types and the presence of CNS metastases.
In patients from the study with exon 19 deletion — a type of EGFR mutation — the median PFS was 20.5 months and 14.1 months in the combination and Tagrisso alone groups, respectively. In patients with L858R mutation from the respective treatment groups, the median PFS was 24.8 months and 18.4 months.
“In our RAMOSE trial, PFS benefit was also observed for [the exon 19 deletion] subgroup as well, with a median PFS of 24.8 months,” the researchers wrote. “Our L858R subgroup had numerically longer PFS than exon 19 deletion subgroup in both [treatment groups], but the difference was not statistically different, likely because of relatively small patient population size.”
Of the 64 patients who had CNS metastases at the beginning of the study, the median PFS was 17.9 months and 13.8 months in the combination and Tagrisso alone groups, respectively. The median PFS for patients without CNS metastases at the beginning was not reached in the combination group and was 18.4 months in the Tagrisso alone group. When the median PFS is not reached, it means that the average amount of patients did not experience disease worsening or spreading at the time of data collection.
Overall, the researchers emphasized that the treatment combination of Cyramza plus Tagrisso was safe and tolerable with good compliance from the patient population.
During the entirety of the trial, there were no reported grade 5 (fatal) side effects. There was only one grade 4 (life-threatening) side effect of hyponatremia occurring in a patient from the combination group, although it was not related to the treatment, researchers noted.
The most common grade 3 (severe) side effects that were observed included diarrhea, fatigue, headache and cough among patients from the combination group. In the Tagrisso alone group, common side effects were diarrhea, fatigue and rash. Grade 3 side effects were observed in 53% versus 41% of patients from the combination and Tagrisso alone groups.
Notable treatment-related side effects from Cyramza included high blood pressure, nose bleeds and high levels of protein in the urine.
Of note, treatment discontinuations because of treatment-related side effects were similar between the two treatment groups, with 9.7% versus 8.7% in the combination and Tagrisso alone groups, respectively.
For patients who received Cyramza, 56 patients were reported to have at least one dose interruption. Common reported reasons for dose interruption were because of high levels of protein in the urine, high blood pressure, reactions to infusions, anemia and abnormally low amounts of platelets.
“There were no major bleeding or clotting events in the RAMOSE trial, and there was no new safety signal,” the researchers wrote. “Overall, patients were highly compliant with 86.6% dose intensity, also indicating excellent safety and tolerability.”
Reference
“A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor–Naïve EGFR-Mutant Metastatic Non–Small Cell Lung Cancer (RAMOSE trial)” by Dr. Xiuning Le, et al., Journal of Clinical Oncology.
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