Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study
Tatsuro Fukuhara,
Haruhiro Saito,
Naoki Furuya,
Kana Watanabe,
Shunichi Sugawara,
Shunichiro Iwasawa,
Yoshio Tsunezuka,
Ou Yamaguchi,
Prof Morihito Okada,
Kozo Yoshimori,
Ichiro Nakachi,
Prof Akihiko Gemma,
Koichi Azuma,
Futoshi Kurimoto,
Yukari Tsubata,
Yuka Fujita,
Hiromi Nagashima,
Gyo Asai,
Satoshi Watanabe,
Masaki Miyazaki,
Prof Koichi Hagiwara,
Prof Toshihiro Nukiwa,
Prof Satoshi Morita,
Prof Kunihiko Kobayashi,
Prof Makoto Maemondo
Affiliations
Tatsuro Fukuhara
Miyagi Cancer Center, Natori, Japan
Haruhiro Saito
Kanagawa Cancer Center, Yokohama, Japan
Naoki Furuya
St. Marianna University School of Medicine, Kawasaki, Japan
Kana Watanabe
Miyagi Cancer Center, Natori, Japan
Shunichi Sugawara
Sendai Kousei Hospital, Sendai, Japan
Shunichiro Iwasawa
Chiba University, Chiba, Japan
Yoshio Tsunezuka
Ishikawa Prefectural Central Hospital, Kanazawa, Japan
Ou Yamaguchi
Saitama Medical University International Medical Center, Hidaka, Japan
Prof Morihito Okada
Hiroshima University Hospital, Hiroshima, Japan
Kozo Yoshimori
Fukujuji Hospital, Tokyo, Japan
Ichiro Nakachi
Saiseikai Utsunomiya Hospital, Utsunomiya, Japan
Prof Akihiko Gemma
Nippon Medical School, Tokyo, Japan
Koichi Azuma
Kurume University, Kurume, Japan
Futoshi Kurimoto
Saitama Cancer Center, Ina, Japan
Yukari Tsubata
Shimane University, Shimane, Japan
Yuka Fujita
National Hospital Organization Asahikawa Medical Center, Asahikawa, Japan
Hiromi Nagashima
Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 2-1-1, Idaidori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan
Gyo Asai
Okazaki City Hospital, Okazaki, Japan
Satoshi Watanabe
Niigata University Medical and Dental Hospital, Niigata, Japan
Masaki Miyazaki
Suita Municipal Hospital, Suita, Japan
Prof Koichi Hagiwara
Jichi Medical University, Shimotsuke, Japan
Prof Toshihiro Nukiwa
Tohoku University, Sendai, Japan
Prof Satoshi Morita
Kyoto University, Kyoto, Japan
Prof Kunihiko Kobayashi
Saitama Medical University International Medical Center, Hidaka, Japan
Prof Makoto Maemondo
Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 2-1-1, Idaidori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan; Corresponding author.
Summary: Background: The NEJ026 Phase 3 study demonstrated that erlotinib and bevacizumab (BE)-treated NSCLC patients with EGFR mutations had significantly better progression-free survival (PFS) than those treated with erlotinib alone (E). This study included a prospective analysis of the relationship between the mutational status of EGFR in plasma circulating tumor DNA (ctDNA) and the efficacy of TKI monotherapy or combination therapy. We describe these results herein. Methods: Plasma samples were collected from patients enrolled in NEJ026 at the start of treatment (P0), 6 weeks after the start of treatment (P1), and upon confirmation of progressive disease (P2). Plasma ctDNA was analyzed using a modified PNA-LNA PCR clamp method. PFS and OS according to EGFR status at the time of plasma collection were evaluated. Findings: Plasma activating EGFR mutation (aEGFR) at P0 was detected in 68% of cases; patients without plasma aEGFR had longer PFS. The frequency of T790M mutation at P2 was similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. Based on the aEGFR profiles, PFS was evaluated among three groups: type A [P0(-), P1(-)], type B [P0(+), P1(-)], and type C [P0(+), P1(+)]. This revealed that BE was more efficacious than E, and that BE was associated with improved PFS in all types. Interpretation: Pre-treatment plasma aEGFR status have a potential of early predictor of response of TKI efficacy. Monitoring plasma aEGFR mutation will contribute to selection and continuation of treatment with BE or E. Funding: Chugai Pharmaceutical.
