Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Targeted-sequencing in rare cancers and the impact on patient treatment.
Developmental Therapeutics and Tumor Biology (Nonimmuno)
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e14755)
Author(s): Hitomi Sumiyoshi Okuma, Takashi Kubo, Hitoshi Ichikawa, Takashi Kohno, Takaaki Mizuno, Yuki Kojima, Kuniko Sunami, Akihiko Shimomura, Satoru Iwasa, Shunsuke Kondo, Yutaka Fujiwara, Kan Yonemori, Kenji Tamura, Noboru Yamamoto; National Cancer Center Hospital, Tokyo, Japan; National Cancer Center Research Institute, Tokyo, Japan; National Cancer Center Research Center, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan; National Cancer Center Hospital East, Tokyo, Japan
Background: Rare cancers lack standard or investigational therapeutic options. Next-generation sequencing (NGS) has provided new insight into personalized medicine. We sought to catalog genetic alterations detected from tissue NGS in rare cancers and to assess their clinical utility. Methods: This was a single-center series with patients (pts) who had been referred to the National Cancer Center Hospital (Tokyo, Japan). Patients with a metastatic/unresectable disease who underwent comprehensive genomic profiling of their tumor for the purpose of precision treatment were first identified (approved by the NCCH institutional review board). Among them, pts diagnosed as rare cancers, defined as an incidence of < 6/100,000 pts/year, were included in this study. Prospectively consentedpts had tissue NGS testing (NCC Oncopanel) for point mutations, select indels, copy number amplifications, fusions. Alterations were assessed for incidence according to cancer type, functional impact, therapeutic implications. Results: Between July 2013 to April 2016, 289 pts were enrolled. 217 pts with sufficient tissue sample succeeded in sequencing. 78% (169/217) had a least one alteration most likely pathogenic. Most common alterations were TP53, PIK3CA, BRCA2, KRAS, MYC, ERBB2, RB1, CCND1, and ARID1A. 114/289 pts (39%) were classified as rare cancers: gynecological cancers (44 pts), cholangiocarcinoma (20), sarcomas (16), NET (9), thymic carc. (6), mesothelioma (3), CUP (2), urachal carc. (2), GIST (1), thyroid carc. (1), other super-rare cancers (10). 86 pts succeeded in sequencing; 72 % (62/86) had a variant most likely pathogenic. Most common alterations were TP53, KRAS, BRCA2, FBXW7, NF1, PIK3CA, ALK, BRCA1, and CCND1. 23 pts (27%) of rare cancer pts received a targeted drug of which 9 (10%) were “matched” to a detected alteration. Response rate to the “matched” therapy was CR/PR/SD/PD = 0/1/5/3 (ORR 11%). Conclusions: Genomic alterations were equally detected in rare cancers as well as common cancers, however showed different alteration profiles. Rare cancer pts receiving “matched” therapy and the response rate to those remain low, suggesting a need for a more efficient treatment development platform. Clinical trial information: UMIN000011141.