Updated analysis: Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802)—Sub-group analysis by KRAS Exon2 status.

Authors

Michio Nakamura

Michio Nakamura

Department of Gastroenterology, Sapporo City General Hospital, Sapporo, Japan

Michio Nakamura , Satoshi Yuki , Kentaro Sawada , Ayane Oba , Atsushi Sato , Takashi Kato , Takashi Meguro , Nobuyuki Ehira , Miki Tateyama , Kazuteru Hatanaka , Kazunori Eto , Hiroyuki Okuda , Yoshimitsu Kobayashi , Osamu Muto , Masakazu Abe , Kanji Kato , Mineo Kudo , Kencho Miyashita , Yuh Sakata , Yoshito Komatsu

Organizations

Department of Gastroenterology, Sapporo City General Hospital, Sapporo, Japan, Hokkaido University Hospital, Sapporo, Japan, Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan, Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan, Department of Internal Medicine, Hokkaido Gastroenterology Hospital, Sapporo, Japan, Department of Gastroenterology, Japanese Red Cross Kitami Hospital, Kitami, Japan, Department of Medical Oncology, Tomakomai Nisshou Hospital, Tomakomai, Japan, Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan, Department of Gastroenterology, Tomakomai City Hospital, Tomakomai, Japan, Department of Medical Oncology, Keiyukai Sapporo Hospital, Sapporo, Japan, Department of Medical Oncology, Japanese Red Cross Akita Hospital, Akita, Japan, Department of Medical Oncology, Sapporo Kosei General Hospital, Sapporo, Japan, Department of Gastroenterology, Iwamizawa Municipal General Hospital, Iwamizawa, Japan, Department of Gastroenterology, Sapporo Hokuyu Hospital, Sapporo, Japan, Department of Gastroenterology, Aiiku Hospital, Sapporo, Japan, Misawa City Hospital, Misawa, Japan, Hokkaido University Hospital Cancer Center, Sapporo, Japan

Research Funding

Other

Background: A few reports have shown the efficacy of bevacizumab (BV) independent of the KRAS Exon2 mutational status (KRAS). We performed a sub-group analysis by KRAS from the HGCSG0802 observational cohort study that investigated 115 patients (pts) treated with 1st line BV for metastatic colorectal cancer (mCRC). Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), response rate (RR), and safety. The key eligibility criteria were with evaluable lesions, older than 20 years, ECOG PS 0-2. In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. Univariate and multivariate analysis for PFS and OS were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 99 pts were evaluable for KRAS. Sixty-two pts (62.6%) had KRAS wild-type (wt) and 37 pts (37.4%) had mutation (mt). The pts characteristics between those with wt and with mt were generally balanced except for PS 0 (91.9% in wt, 75.7% in mt; p = 0.036) and lung metastasis (33.9% in wt, 62.2% in mt; p = 0.007). RR was 70.0% in wt versus 65.7% in mt. Adverse events related to BV were almost balanced except for bleeding (any grade) (30.6% in wt, 13.5% in mt; p = 0.088). The median PFS and OS was 9.9 and 26.8 months in wt versus 7.9 and 17.5 months in mt (PFS ; HR 1.519, p = 0.064 and OS ; HR 1.944, p = 0.005). In Cox multivariate analysis, KRAS mt showed significantly shorter PFS and OS (PFS ; HR 1.637, p = 0.045 and OS ; HR 2.132, p = 0.005). Conclusions: In this cohort, depending on the KRAS Exon2 mutational status, severe adverse events were no significant difference. The multivariate analysis showed that PFS and OS were significantly longer in the KRAS Exon2 wild-type patients. So, KRAS Exon2 mutational status can be a predictive and prognostic marker in bevacizumab combined 1st line chemotherapy. Clinical trial information: UMIN000018935.

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Abstract Details

Meeting

2016 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Cancers of the Colon, Rectum, and Anus

Track

Cancers of the Colon, Rectum, and Anus

Sub Track

Prevention, Diagnosis, and Screening

Clinical Trial Registration Number

UMIN000018935

Citation

J Clin Oncol 34, 2016 (suppl 4S; abstr 522)

DOI

10.1200/jco.2016.34.4_suppl.522

Abstract #

522

Poster Bd #

B13

Abstract Disclosures