Are neutralising anti-VEGF or VEGFR2 antibodies necessary in the treatment of EGFR-mutated non-small-cell lung cancer?
Mené dans 13 pays sur 449 patients atteints d'un cancer du poumon non à petites cellules présentant une mutation EGFR et de stade métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du ramucirumab à l'erlotinib en traitement de première ligne (durée médiane de suivi : 20,7 mois)
The NEJ026 study in patients with EGFR-positive non-small-cell lung cancer (NSCLC) showed that the combination of erlotinib (150 mg/day) plus intravenous bevacizumab (15 mg/kg once every 21 days) yields a median progression-free survival of 16·9 months (95% CI 14·2–21·0) compared with 13·3 months (11·1–15·3) in patients treated with erlotinib alone (p=0·016). The trial was permissive, allowing patients with CNS metastases (32% in each group) and an Eastern Cooperative Oncology Group performance status of 2 or lower to enroll. Median progression-free survival was also longer in patients with Leu858Arg mutations in the erlotinib and bevacizumab group (17·4 months [95% CI 12·6–not estimable]) than in the erlotinib group (13·7 months [8·8–15·5]). However, no significant differences were found between treatment groups in patients with EGFR exon 19 deletions. In The Lancet Oncology, Kazuhiko Nakagawa and colleagues report the results of a phase 3 trial (RELAY) assessing the combination of erlotinib 150 mg/day plus ramucirumab (an anti-VEGFR2 antibody) 10 mg/kg intravenously every 2 weeks versus erlotinib 150 mg/day plus intravenous placebo every 2 weeks. Median progression-free survival was 19·4 months (95% CI 15·4–21·6) in the erlotinib plus ramucirumab group versus 12·4 months (11·0 −13·5) in the erlotinib plus placebo group (hazard ratio 0·59 [95% CI 0·46–0·76], p<0·0001). Grade 3 hypertension occurred in 52 (24%) of the 221 patients in the erlotinib plus ramucirumab group safety population. In the previous NEJ026 study, in the erlotinib plus bevacizumab group, grade 3 hypertension also occurred in 23% of the patients. Both trials shed light on the convenience of combining EGFR tyrosine kinase inhibitors with other drugs. However, several questions arise, because in both trials, the proportion of patients attaining a complete response was very low in the combination group: three (1%) of 224 in RELAY and eight (7%) of 112 in NEJ026.
The Lancet Oncology , commentaire, 2018