Erlotinib plus bevacizumab vs erlotinib monotherapy as first-line treatment for advanced EGFR mutation-positive non-squamous non-small-cell lung cancer: Survival follow-up results of the randomized JO25567 study
Mené au Japon sur 77 et 75 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde EGFR+ de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale à 5 ans, et la toxicité de l'ajout du bévacizumab à l'erlotinib en traitement de première ligne
Objectives : The JO25567 randomized Phase II study demonstrated a statistically significant progression-freesurvival (PFS) benefit with erlotinib plus bevacizumab compared with erlotinib monotherapyin chemotherapy-naïve Japanese patients with epidermal growth factor receptor mutation-positive( EGFR+) non-small-cell lung cancer (NSCLC). Here we present updated PFS and final overallsurvival (OS) data after a median follow-up of 34.7 months. Materials and methods : Patients with stage IIIB/IV or postoperative recurrent NSCLC were randomized to receiveoral erlotinib 150 mg once daily ( n = 77) or erlotinib in combination with intravenous bevacizumab 15 mg/kg every 21days ( n = 75) until disease progression or unacceptable toxicity. OS was analyzed using anunstratified Cox proportional hazards model. Results : Consistent with the primary analysis, addition of bevacizumab to erlotinib was associated with a significant improvement in PFS (hazard ratio [HR] 0.52; 95 % confidence interval[CI]: 0.35–0.76; log-rank two-sided P = 0.0005; median 16.4 months vs 9.8 months, respectively). In contrast, a significant improvement in OS was not seen (HR 0.81; 95 % CI, 0.53–1.23; P = 0.3267; median 47.0 months vs 47.4 months, respectively). Post-study therapy wassimilar between the treatment arms and EGFR mutation type did not affect OS outcomes. The 5-year OS rate was numerically higherwith erlotinib plus bevacizumab vs erlotinib monotherapy (41 % vs 35 %). Updated safetyanalyses confirmed the previously reported manageable tolerability profile, with nonew safety issues. Conclusion : Addition of bevacizumab to first-line erlotinib did not show significant improvementin OS in Japanese patients with stage IIIB/IV or postoperative recurrent EGFR+ NSCLC. Both treatment arms showed a similar median OS benefit (as long as 4 years),irrespective of individual patient characteristics. Results from ongoing studies evaluatingthe combination of EGFR and VEGF signaling inhibitors are eagerly awaited.
Lung Cancer 2020