title: Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling.
abstract: Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44-76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes.
authors.affiliation: St John of God Hospital, Subiaco, WA 6008, Australia.
authors.forename: Andrew
authors.identifier: 0000-0001-6632-2799
authors.initials: A
authors.lastname: Dean
authors.affiliation: St John of God Hospital, Subiaco, WA 6008, Australia.
authors.forename: Aisling
authors.identifier: 0000-0002-8676-3732
authors.initials: A
authors.lastname: Byrne
authors.affiliation: St John of God Hospital, Subiaco, WA 6008, Australia.
authors.forename: Mira
authors.identifier: 0000-0003-3082-1072
authors.initials: M
authors.lastname: Marinova
authors.affiliation: St John of God Hospital, Subiaco, WA 6008, Australia.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hayden
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D057089:Pathology, Molecular
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000077146:Irinotecan; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin