Molecular tumor board assisted care in an advanced cancer population: Results of a phase 2 clinical trial (139)

Megan Hutchcraft; Rachel Miller; Heidi Weiss; Jianrong Wu; Chi Wang; Jinpeng Liu; Rani Jayswal; Mikayla Buchanan; Abigail Anderson; Derek Allison; Riham El Khouli; Lauren Baldwin; Frederick Ueland; Susanne.Arnold Arnold; Jill Kolesar

doi:10.1016/S0090-8258(22)01364-6

Objectives: Multidisciplinary molecular tumor boards (MTBs) interpret next-generation sequencing (NGS) reports to guide treatment decisions. The objective of this study was to compare survival outcomes of advanced cancer patients treated with MTB-directed therapy to immediately prior therapy. Methods: This single-arm prospective phase II clinical trial evaluated the efficacy of MTB-directed targeted cancer treatments. Cancer patients without curative treatment options underwent physician’s choice NGS and were referred to the MTB, which reviewed clinical-pathologic and genomic data. MTB recommended treatments with a tiered level of evidence: - Level 1: FDA-approved / National Comprehensive Cancer Network guideline (level 2A or greater) recommended - Level 2: FDA-approved for alteration in another disease + phase II/III clinical trial evidence in disease of interest - Level 3: FDA-approved for alteration in another disease + case report/phase I clinical trial evidence in disease of interest - Level 4 (not recommended): Mechanistically plausible/preclinical evidence The benefit of MTB-directed therapy was measured by comparing the immediately prior progression-free survival (PFS1) to PFS on MTB-directed therapy (PFS2). The primary outcome was the proportion of patients treated with second or greater line MTB-directed therapy who achieved a PFS ratio ≥1.3 (PFS2/PFS1). A secondary outcome evaluated PFS for patients treated with MTB-directed frontline therapy. We reported exploratory gynecologic cancer results. Results: We enrolled 93 patients, including 13 ovarian and four uterine cancer patients, between January 2017 and October 2020. Gynecologic cancer sites, treatment information, and survival outcomes are detailed in Table 1. PARP (n=7) and immune checkpoint (n=6) inhibitors were frequently recommended. For patients treated with second or greater line MTB-directed therapy (n=50), the Kaplan-Meier estimate of PFS2/PFS1 ≥1.3 was 0.59 (95% CI: 0.47-0.75) and for gynecologic cancer patients (n=14) the estimate was 0.63 (95% CI: 0.44-0.95). For patients treated with front-line MTB-directed therapy (n=43), the median PFS was 449 (range: 42-1125) days. One epithelioid trophoblastic tumor expressed PD-L1; this patient achieved a PFS of 205 days on front-line pembrolizumab. Prior to the Food and Drug Administration (FDA) approval of pembrolizumab for high tumor mutation burden (TMB), a squamous cell carcinoma arising from an ovarian teratoma with a TMB of 25 was treated with pembrolizumab; this patient experienced a PFS of 880 days. The median overall survival on MTB-directed therapy was 768 (range: 22-1240) days. Conclusions: MTB-directed therapy resulted in improved PFS over immediately prior therapy and may be considered for patients with advanced gynecologic malignancies. MTB-directed frontline therapy may benefit patients with rare gynecologic malignancies. Patients with limited treatment options were administered effective therapies ahead of FDA approval. A multidisciplinary approach to molecular profile-directed therapy may be beneficial.

Molecular tumor board assisted care in an advanced cancer population: Results of a phase 2 clinical trial (139)

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