N Yamamoto5, T Seto2, M Nishio3, K Goto4, N Yamamoto5, I Okamoto6, T Yamanaka7, M Tanaka8, K Takahashi9, M Fukuoka10. 1. Wakayama Medical University, Wakayama, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp. 2. National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. Electronic address: setocruise@gmail.com. 3. The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: mnishio@jfcr.or.jp. 4. National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: kgoto@east.ncc.go.jp. 5. National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan. Electronic address: nbryamam@ncc.go.jp. 6. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: okamotoi@kokyu.med.kyushu-u.ac.jp. 7. Faculty of Medicine, Yokohama City University, Kanazawa-ku, Yokohama-shi, Kanagawa, Japan. Electronic address: yamanaka@yokohama-cu.ac.jp. 8. Chugai Pharmaceutical Co. Ltd., Tokyo, Japan. Electronic address: tanaka.misa40@chugai-pharm.co.jp. 9. Chugai Pharmaceutical Co. Ltd., Tokyo, Japan. Electronic address: takahashikuj@chugai-pharm.co.jp. 10. Izumi City General Hospital, Izumi-City, Osaka, Japan. Electronic address: m.fukuoka@tokushukai.jp.
Abstract
OBJECTIVES: The JO25567 randomized Phase II study demonstrated a statistically significant progression-free survival (PFS) benefit with erlotinib plus bevacizumab compared with erlotinib monotherapy in 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 overall survival (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 receive oral erlotinib 150 mg once daily (n = 77) or erlotinib in combination with intravenous bevacizumab 15 mg/kg every 21 days (n = 75) until disease progression or unacceptable toxicity. OS was analyzed using an unstratified 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 was similar between the treatment arms and EGFR mutation type did not affect OS outcomes. The 5-year OS rate was numerically higher with erlotinib plus bevacizumab vs erlotinib monotherapy (41 % vs 35 %). Updated safety analyses confirmed the previously reported manageable tolerability profile, with no new safety issues. CONCLUSION: Addition of bevacizumab to first-line erlotinib did not show significant improvement in 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 evaluating the combination of EGFR and VEGF signaling inhibitors are eagerly awaited. TRIAL REGISTRATION: JapicCTI-111390 and JapicCTI-142569.
RCT Entities:
OBJECTIVES: The JO25567 randomized Phase II study demonstrated a statistically significant progression-free survival (PFS) benefit with erlotinib plus bevacizumab compared with erlotinib monotherapy in 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 overall survival (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 receive oral erlotinib 150 mg once daily (n = 77) or erlotinib in combination with intravenous bevacizumab 15 mg/kg every 21 days (n = 75) until disease progression or unacceptable toxicity. OS was analyzed using an unstratified 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 was similar between the treatment arms and EGFR mutation type did not affect OS outcomes. The 5-year OS rate was numerically higher with erlotinib plus bevacizumab vs erlotinib monotherapy (41 % vs 35 %). Updated safety analyses confirmed the previously reported manageable tolerability profile, with no new safety issues. CONCLUSION: Addition of bevacizumab to first-line erlotinib did not show significant improvement in 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 evaluating the combination of EGFR and VEGF signaling inhibitors are eagerly awaited. TRIAL REGISTRATION: JapicCTI-111390 and JapicCTI-142569.
Authors: Jill F Mentink; Marthe S Paats; Daphne W Dumoulin; Robin Cornelissen; Joris B W Elbers; Alexander P W M Maat; Jan H von der Thüsen; Anne-Marie C Dingemans Journal: Transl Lung Cancer Res Date: 2021-07
Authors: Sung Yong Lee; Chang-Min Choi; Yoon Soo Chang; Kye Young Lee; Seung Joon Kim; Sei Hoon Yang; Jeong Seon Ryu; Jeong Eun Lee; Shin Yup Lee; Ji Young Park; Young-Chul Kim; In-Jae Oh; Chi Young Jung; Sang Hoon Lee; Seong Hoon Yoon; Juwhan Choi; Tae Won Jang Journal: Transl Lung Cancer Res Date: 2021-12