Table 1.
Studies Evaluating Feasibility and Clinical Benefit of Molecular Profiling
| Study | Tumor Types | Screening platform | #Pts sequenced | # Pts on matched therapy | Type of therapy | Endpoint/Results |
|---|---|---|---|---|---|---|
| IMPACT MD Anderson [226] NCT00851032 Retrospective, non-randomized; | All; advanced, refractory | Hotspot sequencing 11 genes; FISH (ALK) | 1144 | 175 | Mono- and combination; Phase I therapies; N.S. | Higher ORR and longer PFS compared to un-matched therapy |
| IMPACT/COMP ACT [48] NCT01505400 Retrospective, observational, non-randomized | Advanced cancers and phase I candidate s | MALDI-TOF MS hotspot panel (23 genes) or targeted NGS panel (48 or 50 genes) | 1640 | 245 | N.S.; investigation al agents of 277 trials including 89 genotype matched trials | Genotyped matched therapy improved response |
| PREDICT [227] NCT02478931 Retrospective, correlative, non-randomized | All; | NGS; (182 or 236 gene panel and 14 or 19 rearrangements | 347 | 87 | N.S. | More patients with SD ≥ 6 month; 45% with extended PFS of 30% compared to previous therapy |
| Bisgrove[228] NCT00530192 Prospective, single-arm Phase I | All; advanced, refractory | IHC, FISH, gene expression | 86 | 68 | Mono- and combination; N.S. | 27% with extended PFS of 30% compared to previous therapy |
| Genomic Profiling in Phase I[46] NCT02437617 Prospective, non-randomized; | All; advanced, refractory | Panel NGS (236 genes); standard biomarker | 339 | 122 | Mono- and combination; Phase I/II therapies; N.S. | High matching score associated with higher SD ≥6 months/PR/CR, longer PFS and survival |
| MOSCATO 01 [44] NCT01566019 Prospective, non-randomized | All; advanced, refractory | CGH array; panel NGS (WES and RNAseq in 2014 included) | 843 | 199 | Phase I drugs and off-label drugs; N.S. | 33% with extended PFS of 30% compared to previous therapy |
| WinTher NCT01856296 Prospective, non-randomized | All; advanced, refractory | DNA (236 genes) and RNA in tumor and normal matched tissue; | To be 200 | N. A. | N.S. Chosen based on DNA analysis, if no actionable mutation, then based on RNA analysis | Estimated completion in 2018 |
| SHIVA [45] NCT01771458 Prospective, randomized | All; advanced, refractory | Panel hotspot NGS (46 genes); CNV | 741 | 99 | erlotinib, lapatinib + trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus | Median PFS in experimental group (matched therapy) not significantly longer than in the control group |
| NCI-MPACT NCT01827384 Prospective, Phase II randomized feasibility study | All, advanced solid tumors | NGS (4000 variants across 143 genes); Activation of RAS/RAF or PI3K pathway; Inactivation of DNA repair pathway; | To be 700 | N.A. | Carboplatin, Everolimus, Temozolomi de, Trametinib, Veliparib, AZD1775 | Estimated completion in 2019; Outcome measures: ORR; compare genotype matched vs physicians choice |
AZD1775, WEE1 inhibitor; IHC, Immunohisochemistry; NGS, next generation sequencing; FISH, fluorescent in situ hybridization; PFS, progression free survival; ORR, overall response rate; SD, stable disease; PR, partial response; CR, complete response; CGH, comparative genomic hybridization; WES, whole exome sequencing; N.A., not applicable; N.S., not specified; Pts, patients;