Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board

Abstract

Purpose: Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice.

Methods: A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration-approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing.

Results: One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months (95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43%(95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports.

Conclusion: The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.

Fig 1.

Genetic Alterations in Tumors With Actionable Yields (GAITWAY) tumor board approach to therapeutic recommendations on the basis of tumor genomic analyses. GA, genomic alteration.

Fig 2.

Frequency of genomic alterations. Actionable genomic alterations and selected nonactionable alterations are shown. For actionable genes, the number of patients in whom an action was taken is shown. Actions taken included therapy assignment, germline testing, or microsatellite instability evaluation.

Fig 3.

CONSORT diagram of patients discussed at the molecular tumor board. Note, all numbers do not add up because some patients are counted in more than one category (eg, had an actionable alteration for a clinical trial and also were recommended off-label use or had an actionable alteration for therapy and also for germline analysis). (*) One patient with KRAS mutation for whom the board recommended a clinical trial only but who was prescribed off-label trametinib by his primary oncologist. FDA, US Food and Drug Administration; NED, no evidence of disease; PS, performance status.

Fig 4.

(A) Progression-free survival (PFS) of patients treated with genomically matched therapy (n = 22) or nonmatched therapy (n = 54). All patients with follow-up who were treated with genomically matched therapy are included in the analysis, including one patient who was treated with off-label trametinib for a KRAS mutation when the board had recommended a clinical trial. (B) PFS and PFS on immediate prior therapy for individual patients treated with genomically matched therapies. Eight patients either had no prior systemic therapy for metastatic disease or insufficient documentation of prior therapy. Arrowheads indicate patients continuing on treatment. amp, amplification; CR, complete response; ER, estrogen receptor; PR, partial response; SD, stable disease; TNBC, triple-negative breast cancer.