Molecular Tumor Board-Assisted Care in an Advanced Cancer Population: Results of a Phase II Clinical Trial

Rachel W Miller, Megan L Hutchcraft, Heidi L Weiss, Jianrong Wu, Chi Wang, Jinpeng Liu, Rani Jayswal, Mikayla Buchanan, Abigail Anderson, Derek B Allison, Riham H El Khouli, Reema A Patel, John L Villano, Susanne M Arnold, Jill M Kolesar, Rachel W Miller, Megan L Hutchcraft, Heidi L Weiss, Jianrong Wu, Chi Wang, Jinpeng Liu, Rani Jayswal, Mikayla Buchanan, Abigail Anderson, Derek B Allison, Riham H El Khouli, Reema A Patel, John L Villano, Susanne M Arnold, Jill M Kolesar

Abstract

Purpose: Multidisciplinary molecular tumor boards (MTBs) interpret next-generation sequencing reports and help oncologists determine best therapeutic options; however, there is a paucity of data regarding their clinical utility. The purpose of this study was to determine if MTB-directed therapy improves progression-free survival (PFS) over immediately prior therapy in patients with advanced cancer.

Methods: This single-arm, prospective phase II clinical trial enrolled patients with advanced cancer with an actionable mutation who received MTB-recommended targeted therapy between January 1, 2017, and October 31, 2020. MTB-recommended both on-label (level 1 evidence) and off-label (evidence levels 2 and 3) therapies. Of the 93 enrolled patients, 43 were treated frontline and 50 received second-line or greater-line therapy. The primary outcome was the probability of patients treated with second-line or greater-line MTB-directed therapy who achieved a PFS ratio ≥ 1.3 (PFS on MTB-directed therapy divided by PFS on the patient's immediately prior therapy). Secondary outcomes included PFS for patients treated frontline and overall survival and adverse effects for the entire study population.

Results: The most common disease sites were lung (35 of 93, 38%), gynecologic (17 of 93, 18%), GI (16 of 93, 17%), and head and neck (7 of 93, 8%). The Kaplan-Meier estimate of the probability of PFS ratio ≥ 1.3 was 0.59 (95% CI, 0.47 to 0.75) for patients treated with second-line or greater-line MTB-directed therapy. The median PFS was 449 (range 42-1,125) days for patients treated frontline. The median overall survival was 768 (range 22-1,240) days. There were four nontreatment-related deaths.

Conclusion: When treated with MTB-directed therapy, most patients experienced improved PFS compared with immediately prior treatment. MTB-directed targeted therapy may be a strategy to improve outcomes for patients with advanced cancer.

Trial registration: ClinicalTrials.gov NCT03089554.

Conflict of interest statement

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).

Figures

FIG 1.
FIG 1.
Study flow diagram. Flow diagram shows identification of patients who underwent MTB review and subsequent enrollment in this trial. MCC, Markey Cancer Center; MTB, molecular tumor board.
FIG 2.
FIG 2.
Genomic profiles, recommendations, and MTB-directed targeted therapy, and outcomes of patients enrolled in this trial. Genes and biomarkers are displayed in columns. Rows demonstrate individual tumor profiles, targeted therapy, and PFS ratio for each patient. GYN, gynecologic; LOH, loss of heterozygosity; MSI, microsatellite instability; MTB, molecular tumor board; PD-L1: programmed death-ligand 1; PFS, progression-free survival; TMB, tumor mutational burden.
FIG 3.
FIG 3.
Growth modulation index among patients treated with second-line or greater-line MTB-directed therapy (cohort 1; n = 50). (A) GMI analysis for 50 patients who had prior therapy PFS data. Larger GMI values represent higher PFS2/PFS1 ratios, indicating superior PFS on MTB-directed therapy (PFS2). Survival probability indicates the probability of obtaining or exceeding a particular GMI. A GMI ≥ 1.3 suggests the benefit of subsequent therapy. The simple proportion of patients experiencing GMI ≥ 1.3 (27 of 50) is 0.54. To provide an accurate estimation, the Kaplan-Meier method accounts for censoring of PFS2 and is 0.59. The Hall-Wellner band indicates the 95% CI, 0.466 to 0.746. (B) Individual patients' time to progression (days) on prior therapy (x axis) and MTB-directed therapy (y axis) is delineated by a circle. The blue line indicates GMI = 1.3. Patients to the left of the blue line demonstrated the most benefit from MTB-directed therapy with some long-term survivors. The red line indicates GMI = 1.0. Patients with GMI = 1.0 conferred the same benefit from MTB-directed therapy as they with their most recent therapy. GMI, growth modulation index; MTB, molecular tumor board; PFS, progression-free survival; TTP, time to progression.
FIG 4.
FIG 4.
Waterfall plot detailing individual PFS ratio (PFS2/PFS1) values for patients treated with second-line or greater-line MTB-directed therapy (cohort 1; n = 50). A larger PFS2/PFS1 value indicates a greater benefit of MTB-directed therapy. MTB, molecular tumor board; PFS, progression-free survival.

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