Table 1:
Examples of Precision Medicine Trials: Design and Outcomes
| Year First/Last author | Trial name | Trial type | No of pts screened (N) | Proportion of pts. matched | Biomarker(s) | Outcome | Institute(s) | Comments |
|---|---|---|---|---|---|---|---|---|
| Diverse treatment-refractory tumor types | ||||||||
| 20101 Von Hoff D Penny R | Bisgrove | Prospective, navigational | 86 | 77% | IHC, FISH, microarray | 27% of 66 matched pts had a PFS2/PFS1 ratio* ≥1.3 (95% CI, 17% to 38%; p = 0.007). | US (9 sites) | |
| 20122 Tsimberidou A Kurzrock R | IMPACT, first cohort | Registry type, Navigational | 1144 | 15% | PCR-based genomics, 9 genes |
Matched vs unmatched RR, 27% vs. 5% (p<0.0001), TTF: median, 5.2 vs. 2.2 mos (p<0.0001) OS: median, 13.4 vs. 9.0 mos (p = 0.017) |
MD Anderson Cancer Center | |
| 20143 Tsimberidou A Berry D | IMPACT, second cohort | Registry type, navigational | 1276 | 11% | PCR-based genomics, 18–50 genes |
Matched vs unmatched RR, 11.9% vs. 5% (p<0.0001), PFS: median, 3.9 vs. 2.2 mos, (p=0.001); OS: median, 11.4 vs. 8.6 mos (p=0.04) |
MD Anderson Cancer Center | 2-month landmark analyses, matched therapy group: OS, responders 30.5 months vs. 11.3 months for non-responders (p = 0.01). |
| 20174 Tsimberidou AM Kurzrock R | IMPACT, third cohort | Registry type, navigational | 1436 | 27% | PCR-based genomics and NGS, 11 to 182 genes |
Matched vs unmatched Higher rates of ORR (p=0.0099), TTF (p=0.0015), and OS (p=0.04) |
MD Anderson Cancer Center | |
| 20155 Le Tourneau Paoletti X | SHIVA | Prospective, randomized | 741 | 13% | Targeted NGS, ~50 genes | PFS not improved with matched therapy (p=0.41) | Institut Curie, 8 French sites | ~80% of patients received single-agent hormone modulators or everolimus |
| 20166 Schwaederle M Kurzrock R | PREDICT | Registry type | 347 | 25% | NGS, 182 or 236 genes |
Matched vs unmatched Higher rates of SD≥ 6 months/PR/CR (p=0.02) and PFS (p<0.04). Higher matching scores correlated with better OS: 15.7 vs 10.6 mos (p=0.04) |
University of California San Diego | |
| 20167 Wheler JJ Kurzrock R | MD Anderson Personalized Cancer Therapy Initiative | Prospective, navigational | 500 | 24% | NGS, 236 genes | Higher matching scores correlated with higher rates of SD ≥6 months/PR/CR (p=0.024), TTF (p=0.0003), and OS (p=0.05) | MD Anderson Cancer Center | |
| 20168 Stockley TL Bedard PL | IMPACT/COMPACT | Prospective | 1893 | 5% | Hot spot panel, 23 genes |
Matched vs unmatched Higher ORR: 19% vs 9%, (p=0.026). |
Princess Margaret, Canadian centers |
|
| 20179 Massard C Soria JC | MOSCATO | Prospective | 1035 | 19% | Targeted NGS, 40–75 genes; aCGH; RNAseq | PFS2/PFS1 ratio* was >1.3 in 33% (63/193) of patients | Institut Gustave Roussy |
|
| 201810 Hainsworth JD Kurzrock R | MyPathway | Prospective, Phase 2 basket | 251 | Not available | Genomic testing via any CLIA lab | Matched patients, ORR: All, 23% HER2-altered, 38% BR4F-altered, 43% |
Multiple sites, Genentech | 251 patients enrolled; 230 were treated; however, how many were screened pre-enrollment is unknown |
| 201911 Tredan O Blay JY | Profiler | Prospective | 2579 | 6% | NGS, 69 genes | RR = 13% (23 of 182 treated) | Four institutes (France) | |
| 201912 Sicklick J Kurzrock R | I-PREDICT | Prospective, navigational | 149 | 49% | NGS, 315 genes; ctDNA; PDL1 IHC | Higher matching scores correlated with increased rates of SD≥6 months/PR/CR: 50% vs 22.4% (p=0.028), PFS (p=0.0004), and OS (p=0.038) | University of California San Diego and Avera | First trial to administer customized combination therapy (“N-of-1” matching) |
| 201913 Rodon J Kurzrock R | WINTHER | Prospective, navigational | 303 | 35% | NGS, 236 genes; transcriptomics | Higher matching scores correlated with longer PFS (p=0.005) and OS (p= 0.03) | Five countries (Spain, Israel, France, Canada, US) | First solid tumor trial to include transcriptomics |
| Specific tumors—Lung | ||||||||
| 201114 Kim ES Hong WK | BATTLE | Prospective, adaptive, randomized | 255 | Not available | 11 biomarkers | 8-week disease control rate, 46% | MD Anderson Cancer Center | It is unclear how many patients were screened before consent |
| 201415 Kris MG Bunn PA | Lung cancer mutation consortium | Prospective | 1537 | 17% | Multiplex genotyping, 10 genes | Improved OS with matched vs unmatched therapy (p=0.006) | 14 US sites | |
| 201616 Aisner D Kwiatkowski DJ | Lung Cancer Mutation Consortium II | Prospective | 904 | 12% | NGS, minimum of 14 genes | Improved survival with matched therapy (p<0.001) | 16 sites | |
| 201617 Papadimitrakopoulou V Herbst RS | BATTLE-2 | Prospective, adaptive, randomized | 334 | Non-applicable | ALK, FISH, EGFR, and KRAS Sanger sequencing | KRAS alterations: longer PFS without erlotinib (p=0.04); KRAS wild-type tumors: longer OS on erlotinib (p=0.03) | MD Anderson Cancer Center | |
| Specific tumors—Breast | ||||||||
| 201218 Esserman LJ Hylton N | I-SPY 1 | Neoadjuvant, correlative | 237 | Non-applicable | IHC | pCR differs by subset | Multiple US sites | Aim was to develop biomarkers of response to conventional therapy |
| 201519 Andre F Bonnefoi H | SAFIR01/UNICANCER | Prospective | 423 | 13% | Sanger sequencing (2 genes: PIK3CA and AKT); aCGH | Matched group, ORR 9% | 18 centers in France | |
| 201620,21 Park JW Berry DA Rugo HS Esserman LJ |
I-SPY 2 | Phase 2 adaptive design, neoadjuvant | Non-applicable | Non-applicable | IHC, Mammaprint | Improved pCR rates in 2 study arms with drug addition: HER2+, hormone receptor-negative: neratinib plus standard therapy (N=115) vs standard therapy (N=78): 56% vs 33% Triple-negative: veliparib plus carboplatin (N=72) with standard therapy vs standard therapy (N=44): 51% vs 26% |
Quantum-Leap Healthcare (US sites) | Results for 2 arms of I-SPY-2 study available |
| Specific tumors—Gastric | ||||||||
| 2019122 Lee J WK Kang | VICTORY | Prospective | 772 | 14% | NGS, IHC, PDL1, MMR and EBV status | Improved PFS and OS with matched vs unmatched therapy (p<0.0001) | Republic of Korea | The trial included 10 phase II trials that operated independently (based on eight biomarkers) |
*
PFS2/PFS1 ratio is defined by the PFS on the trial versus the PFS on the therapy immediately preceding the trial; in general, PFS is shorter with every subsequent therapy
**
Only studies published as manuscripts, not just as abstracts, included
Abbreviations:aCGH=array comparative genomic hybridization, ASCO=American Society of Clinical Oncology, CLIA=clinical laboratory improvement amendment, cDNA MA=cDNA microarray, CGP=comprehensive genomic profiling, CR=complete remission, ctDNA=circulating tumor DNA, FISH=fluorescence in situ hybridization, IHC=immunohistochemistry, mos=months, NGS=next-generation sequencing, ORR=overall response rate, OS=overall survival, pCR=pathological complete response, PCR=polymerase chain reaction, PFS=progression-free survival, PR=partial remission; pts=patients, RR=response rate, RRPA=reverse phase protein array, SD=stable disease, TTF=time to treatment failure