title: Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study.
abstract: This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.3. The null hypothesis was that ≤ 15% of patients gain such benefit. Overall, ≥ 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥ 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.
authors.affiliation: Department of Oncology, Rambam Health Care Campus, 3109601 Haifa, Israel ; Facutly of Medicine, Technion-Israel Institute of Technology, 3525406 Haifa, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Epelbaum
authors.affiliation: Division of Oncology, Sheba Medical Center Tel Hashomer, 5262100 Ramat-Gan, Israel ; Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Shacham-Shmueli
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Department of Oncology, Assuta Hospital, 6971028 Tel Aviv, Israel ; Department of Oncology, Meir Medical Center, 4428164 Kfar Saba, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Klein
authors.affiliation: Department of Oncology, Rambam Health Care Campus, 3109601 Haifa, Israel.
authors.forename: Abed
authors.initials: A
authors.lastname: Agbarya
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Davidoff Center, Rabin Medical Center, 4941492 Petah Tikva, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Brenner
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Department of Oncology, Wolfson Hospital, 5822012 Holon, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Brenner
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Division of Oncology, Tel-Aviv Sourasky Medical Center, 6423906 Tel Aviv, Israel.
authors.forename: Eliahu
authors.initials: E
authors.lastname: Gez
authors.affiliation: Division of Oncology, Sheba Medical Center Tel Hashomer, 5262100 Ramat-Gan, Israel ; Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Golan
authors.affiliation: Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, 9124001 Jerusalem, Israel ; The Hebrew University Hadassah Medical School, 9112102 Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Davidoff Center, Rabin Medical Center, 4941492 Petah Tikva, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Purim
authors.affiliation: Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, 9124001 Jerusalem, Israel ; The Hebrew University Hadassah Medical School, 9112102 Jerusalem, Israel.
authors.forename: Mark
authors.initials: M
authors.lastname: Temper
authors.affiliation: Department of Oncology, Assuta Hospital, 6971028 Tel Aviv, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Tepper
authors.affiliation: Caris Life Sciences, 4052 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Voss
authors.affiliation: Caris Life Sciences, 4052 Basel, Switzerland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Russell
authors.affiliation: Oncotest-Teva Pharmaceutical Industries, Ltd., 60850 Shoham, Israel.
authors.forename: Addie
authors.initials: A
authors.lastname: Dvir
authors.affiliation: Oncotest-Teva Pharmaceutical Industries, Ltd., 60850 Shoham, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Soussan-Gutman
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Davidoff Center, Rabin Medical Center, 4941492 Petah Tikva, Israel.
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.affiliation: Sackler Medical School, Tel Aviv University, 6997801 Tel Aviv, Israel ; Division of Oncology, Tel-Aviv Sourasky Medical Center, 6423906 Tel Aviv, Israel.
authors.forename: Ravit
authors.initials: R
authors.lastname: Geva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor