Next-Generation Sequencing of Advanced GI Tumors Reveals Individual Treatment Options.

Purpose: Precision oncology connects highly complex diagnostic procedures with patient histories to identify individualized treatment options in interdisciplinary molecular tumor boards (MTBs). Detailed data on MTB-guided treatments and outcome with a focus on advanced GI cancers have not been reported yet.
Patients and Methods: Next-generation sequencing of tumor and normal tissue pairs was performed between April 2016 and February 2018. After identification of relevant molecular alterations, available clinical studies or in-label, off-label, or matched experimental treatment options were recommended. Follow-up data and a response assessment that was based on radiologic imaging were recorded.
Results: Ninety-six patients were presented to the MTB of Tuebingen University Hospital. Sixteen (17%) showed "pathogenic" or "likely pathogenic" germline variants. Recommendations on the basis of molecular alterations or tumor mutational burden were given for 41 patients (43%). Twenty-five received the suggested drug, and 20 were evaluable for best response assessment. Three patients (15%) reached a partial response (PR), and 6 (30%), stable disease (SD), whereas 11 (55%) had tumor progression (progressive disease). Median progression-free survival (PFS) for all treated and evaluable patients was 2.8 months (range, 1.0-9.0 months), and median overall survival (OS) of all treated patients was 5.2 months (range, 0.1 months to not reached). Patients with SD for ≥ 3 months or PR compared with progressive disease showed both a statistically significant longer median PFS (7.8 months [95% CI, 4.2 to 11.4 months] v 2.2 months [95% CI, 1.5 to 2.8 months], P < .0001) and median OS (18.0 months [95% CI, 10.4 to 25.6 months] v 3.8 months [95% CI, 2.3 to 5.4 months], P < .0001).
Conclusion: Next-generation sequencing diagnostics of advanced GI cancers identified a substantial number of pathogenic or likely pathogenic germline variants and unique individual treatment options. Patients with PR or SD in the course of MTB-recommended treatments seemed to benefit with respect to PFS and OS.
Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Michael BitzerConsulting or Advisory Role: Bristol-Myers Squibb, Bayer Vital GmbH, EISAI, Ipsen, Lilly Travel, Accommodations, Expenses: Ipsen, CelgeneSaskia BiskupEmployment: CeGaT Stock and Other Ownership Interests: CeGaTMartin SchulzeEmployment: Praxis für Humangenetik TuebingenFranz HilkeHonoraria: Agilent Technologies Research Funding: Novartis (Inst) Travel, Accommodations, Expenses: Agilent TechnologiesKonstantin NikolaouHonoraria: Siemens Healthineers, Bayer Schering Pharma Consulting or Advisory Role: Siemens Healthineers Speakers' Bureau: Siemens Healthineers Research Funding: Siemens Healthineers (Inst), Bayer Schering Pharma (Inst) Travel, Accommodations, Expenses: Siemens Healthineers, Bayer Schering PharmaChristopher SchroederResearch Funding: Illumina (Inst), Novartis (Inst)Olaf RiessHonoraria: AstraZeneca, Takeda/Shire Consulting or Advisory Role: Illumina Research Funding: Illumina (Inst)Falko FendConsulting or Advisory Role: Roche, EUSA PharmaDaniel ZipsResearch Funding: Elekta (Inst), Siemens (Inst), Sennewald (Inst) Travel, Accommodations, Expenses: Elekta (Inst)Martina HinterleitnerTravel, Accommodations, Expenses: Novartis/IpsenLars ZenderLeadership: HeparegeniX GmBH Consulting or Advisory Role: Boehringer Ingelheim Research Funding: HeparegeniX GmBH Patents, Royalties, Other Intellectual Property: Patent on MKK4 Inhibition for the treatment of acute and chronic liver diseases Travel, Accommodations, Expenses: IpsenGhazaleh TabatabaiHonoraria: AbbVie, Bayer, Medac, Novocure (Inst) Consulting or Advisory Role: AbbVie, Bayer Travel, Accommodations, Expenses: Novocure (Inst)Nisar P. MalekHonoraria: Spring Bank Travel, Accommodations, Expenses: Falk Foundation No other potential conflicts of interest were reported.
(© 2020 by American Society of Clinical Oncology.)