Match!

Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study

Published on May 20, 2017in Journal of Clinical Oncology28.349
· DOI :10.1200/PO.17.00002
Apostolia Maria Tsimberidou50
Estimated H-index: 50
(University of Texas MD Anderson Cancer Center),
David K. Hong54
Estimated H-index: 54
(University of Texas MD Anderson Cancer Center)
+ 15 AuthorsRazelle Kurzrock99
Estimated H-index: 99
(UCSD: University of California, San Diego)
Sources
Abstract
PurposeGenomic profiling is increasingly used in the management of cancer. We have previously reported preliminary results of our precision medicine program. Here, we present response and survival outcomes for 637 additional patients who were referred for phase I trials and were treated with matched targeted therapy (MTT) when available.Patients and MethodsPatients with advanced cancer who underwent tumor genomic analyses were treated with MTT when available.ResultsOverall, 1,179 (82.1%) of 1,436 patients had one or more alterations (median age, 59.7 years; men, 41.2%); 637 had one or more actionable aberrations and were treated with MTT (n = 390) or non-MTT (n = 247). Patients who were treated with MTT had higher rates of complete and partial response (11% v 5%; P = .0099), longer failure-free survival (FFS; 3.4 v 2.9 months; P = .0015), and longer overall survival (OS; 8.4 v 7.3 months; P = .041) than did unmatched patients. Two-month landmark analyses showed that, for MTT patients, FFS for responders v...
Figures & Tables
  • References (24)
  • Citations (17)
📖 Papers frequently viewed together
374 Citations
297 Citations
130 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References24
Newest
#1Christophe Le Tourneau (Curie Institute)H-Index: 25
#2Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
The SHIVA trial compared the efficacy of targeted agents selected on the basis of tumour molecular profiling (using an algorithmic approach) with that of physician's choice across multiple solid tumours; the trial was negative for the primary end point. We now discuss the challenges associated with precision medicine trial design and propose solutions learned from this trial.
11 CitationsSource
#1Jennifer J. Wheler (University of Texas MD Anderson Cancer Center)H-Index: 32
#2Filip JankuH-Index: 41
Last. Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
view all 19 authors...
TP53 tumor suppressor gene mutations are amongst the most frequent abnormalities in cancer, affecting approximately 40% of patients. Yet, there is no accepted way to target these alterations in the clinic. At the same time, antagonists of vascular endothelial growth factor (VEGF) receptor (VEGFR) or its ligand are best-selling oncology drugs, with multiple, expensive compounds approved. While only a subset of patients benefit from these anti-angiogenesis agents, no relevant biomarker has been id...
19 CitationsSource
#1Jennifer J. Wheler (University of Texas MD Anderson Cancer Center)H-Index: 32
#2Filip JankuH-Index: 41
Last. Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
view all 19 authors...
71 CitationsSource
#1Maria Schwaederle (UCSD: University of California, San Diego)H-Index: 18
#2Barbara A. Parker (UCSD: University of California, San Diego)H-Index: 52
Last. Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
view all 12 authors...
By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next-generation sequencing (NGS) results were evaluated. Outcomes for patients who received a “matched” versus “unmatched” therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a “matched” therapy, 93 (26.8%) with an “unmatched”...
47 CitationsSource
#1K. Koehler (OSU: Ohio State University)H-Index: 1
#2David A. Liebner (OSU: Ohio State University)H-Index: 12
Last. J. L. Chen (OSU: Ohio State University)H-Index: 1
view all 3 authors...
To investigate whether TP53 DNA mutational status impacts progression-free survival (PFS) in patients with advanced sarcomas (soft tissue sarcoma) treated with vascular endothelial growth factor receptors (VEGFR) inhibition.We retrospectively reviewed 19 cases of patients treated at the Ohio State James Comprehensive Cancer Center with advanced sarcoma treated with VEGFR inhibition who also had next-generation sequencing of their tumors (via FoundationOne Heme panel). We evaluated TP53 as well a...
21 CitationsSource
#1Apostolia Maria Tsimberidou (University of Texas MD Anderson Cancer Center)H-Index: 50
#2Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
25 CitationsSource
#1Christophe Le Tourneau (Curie Institute)H-Index: 25
#2Jean-Pierre DelordH-Index: 31
Last. Xavier Paoletti (Curie Institute)H-Index: 32
view all 23 authors...
374 CitationsSource
#1Maria Schwaederle (UCSD: University of California, San Diego)H-Index: 18
#2Gregory A. Daniels (UCSD: University of California, San Diego)H-Index: 24
Last. Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
view all 8 authors...
Despite the increased use of molecular diagnostics, the extent to which patients who have these tests harbor potentially actionable aberrations is unclear. We retrospectively reviewed 439 patients with diverse cancers, for whom next-generation sequencing (mostly 236-gene panel) had been performed. Data pertaining to the molecular alterations identified, as well as associated treatment suggestions (on- or off-label, or experimental), were extracted from molecular diagnostic reports. Most patients...
41 CitationsSource
#1Maria Schwaederle (UCSD: University of California, San Diego)H-Index: 18
#2Vladimir LazarH-Index: 46
Last. Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
view all 8 authors...
Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptom...
36 CitationsSource
#1Sandip Pravin Patel (UCSD: University of California, San Diego)H-Index: 16
#2Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
The resurgence of cancer immunotherapy stems from an improved understanding of the tumor microenvironment. The PD-1/PD-L1 axis is of particular interest, in light of promising data demonstrating a restoration of host immunity against tumors, with the prospect of durable remissions. Indeed, remarkable clinical responses have been seen in several different malignancies including, but not limited to, melanoma as well as lung, renal and bladder cancer. Even so, determining which patients derive bene...
508 CitationsSource
Cited By17
Newest
#1B Westphalen (LMU: Ludwig Maximilian University of Munich)
#2Carsten Bokemeyer (UHH: University of Hamburg)H-Index: 78
Last. Ulrich Keilholz (Humboldt University of Berlin)H-Index: 2
view all 63 authors...
Abstract Precision cancer medicine (PCM) holds great promises to offer more effective therapies to patients based on molecular profiling of their individual tumours. Although the PCM approach seems intuitive, multiple conceptional and structural challenges interfere with the broad implementation of PCM into clinical practice. Accordingly, concerted national and international efforts are needed to guide the further development and broad adoption of PCM in Germany. With support of the ‘German Canc...
Source
#1Apostolia Maria Tsimberidou (University of Texas MD Anderson Cancer Center)H-Index: 50
#2Sheryl K. ElkinH-Index: 8
view all 4 authors...
Abstract Two recent studies examining the clinical and economic value of next-generation sequencing (NGS)-based diagnostic testing (multi-gene panel examining > 30 genes) for non-small cell lung cancer therapy compared to single gene ALK, EGFR testing to select therapy demonstrated statistically insignificant improvement in population-level overall survival (OS) and only a moderate incremental cost effectiveness ratio associated with the NGS testing approach. The data, however, revealed a key pr...
Source
#1Aude Collignon (AMU: Aix-Marseille University)
#3Camille Montersino (AMU: Aix-Marseille University)H-Index: 2
Last. José Adélaïde (AMU: Aix-Marseille University)H-Index: 50
view all 20 authors...
Targeted next-generation sequencing (tNGS) and ex vivo drug sensitivity/resistance profiling (DSRP) have laid foundations defining the functional genomic landscape of acute myeloid leukemia (AML) and premises of personalized medicine to guide treatment options for patients with aggressive and/or chemorefractory hematological malignancies. Here, we have assessed the feasibility of a tailored treatment strategy (TTS) guided by systematic parallel ex vivo DSRP and tNGS for patients with relapsed/re...
Source
#1Alex H. Wagner (WashU: Washington University in St. Louis)H-Index: 10
#3Brian Walsh (OHSU: Oregon Health & Science University)H-Index: 2
Last. Jianjiong Gao (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 52
view all 39 authors...
Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggre...
Source
#1Anne Hansen Ree (University of Oslo)H-Index: 24
#2Vigdis Nygaard (Oslo University Hospital)H-Index: 9
Last. Marius Lund-Iversen (Oslo University Hospital)H-Index: 13
view all 25 authors...
Background: In precision cancer medicine, the challenge is to prioritize DNA driver events, account for resistance markers, and procure sufficient information for treatment that maintains patient safety. The MetAction project, exploring how tumor molecular vulnerabilities predict therapy response, first established the required workflow for DNA sequencing and data interpretation (2014-2015). Here, we employed it to identify molecularly matched therapy and recorded outcome in end-stage cancer (20...
Source
#2Radhamani Kannaiyan (Vidant Medical Center)
Last. Daruka MahadevanH-Index: 32
view all 6 authors...
Matched-targeted and immune checkpoint therapies have improved survival in cancer patients, but tumor heterogeneity contributes to drug resistance. Our study categorized gene mutations from next generation sequencing (NGS) into three core processes. This annotation helps decipher complex biologic interactions to guide therapy. We collected NGS data on 145 patients who have failed standard therapy (2016 to 2018). One hundred and forty two patients had data for tissue (Caris MI/X) and plasma cell-...
Source
#1Michael J. Pishvaian (University of Texas MD Anderson Cancer Center)H-Index: 10
#2Edik M. BlaisH-Index: 6
Last. Davendra Sohal (UC: University of Cincinnati)H-Index: 1
view all 16 authors...
Summary Background About 25% of pancreatic cancers harbour actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) programme includes US patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. We sought to determine whe...
3 CitationsSource
#1Nicole L. Michmerhuizen (UM: University of Michigan)H-Index: 5
#2John H. Owen (UM: University of Michigan)H-Index: 11
Last. J.C. Brenner (UM: University of Michigan)H-Index: 4
view all 11 authors...
Chordomas are rare and serious tumors with few effective treatments outside of aggressive surgery and radiation. Targeted therapies may present a more effective option for a subset of patients with lesions possessing certain genetic biomarkers. A small molecule inhibitor library was tested in patient-derived UM-Chor1 cells to identify targeted therapies with potential efficacy. Targeted exome sequencing of UM-Chor1 and UM-Chor2 cells was performed to investigate genetic aberrations in relevant p...
Source
#1Marc R. Matrana (UQ: University of Queensland)H-Index: 10
Background: Clinical research studies often integrate precision medicine technologies and techniques, offering novel treatment opportunities for patients but also posing significant challenges for regulatory authorities and local institutional review boards (IRBs) as they attempt to protect patient safety and privacy. Methods: We review the basics of precision medicine and discuss how IRBs are addressing new challenges associated with the era of precision medicine. Results: Precision medicine tr...
Source
#1Apostolia Maria Tsimberidou (University of Texas MD Anderson Cancer Center)H-Index: 50
#2David K. Hong (University of Texas MD Anderson Cancer Center)H-Index: 54
Last. Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
view all 13 authors...
In 2007, we initiated IMPACT, a precision medicine program for patients referred for participation in early-phase clinical trials. We assessed the correlation of factors, including genomically matched therapy, with overall survival (OS). We performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes ≤ 182) for patients with lethal/refractory advanced cancers referred to the Phase 1 Clinical Trials Program. Matched therapy, if available, was selected on the basis of genomics...
1 CitationsSource