Details

Autor(en) / Beteiligte

• Lopez-Chavez, Ariel
• Thomas, Anish
• Rajan, Arun
• Raffeld, Mark
• Morrow, Betsy
• Kelly, Ronan
• Carter, Corey Allan
• Guha, Udayan
• Killian, Keith
• Lau, Christopher C
• Abdullaev, Zied
• Xi, Liqiang
• Pack, Svetlana
• Meltzer, Paul S
• Corless, Christopher L
• Sandler, Alan
• Beadling, Carol
• Warrick, Andrea
• Liewehr, David J
• Steinberg, Seth M
• Berman, Arlene
• Doyle, Austin
• Szabo, Eva
• Wang, Yisong
• Giaccone, Giuseppe

Titel

Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial

Ist Teil von

• Journal of clinical oncology, 2015-03, Vol.33 (9), p.1000-1007

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• We conducted a basket clinical trial to assess the feasibility of such a design strategy and to independently evaluate the effects of multiple targeted agents against specific molecular aberrations in multiple histologic subtypes concurrently. We enrolled patients with advanced non-small-cell lung cancer (NSCLC), small-cell lung cancer, and thymic malignancies who underwent genomic characterization of oncogenic drivers. Patients were enrolled onto a not-otherwise-specified arm and treated with standard-of-care therapies or one of the following five biomarker-matched treatment groups: erlotinib for EGFR mutations; selumetinib for KRAS, NRAS, HRAS, or BRAF mutations; MK2206 for PIK3CA, AKT, or PTEN mutations; lapatinib for ERBB2 mutations or amplifications; and sunitinib for KIT or PDGFRA mutations or amplification. Six hundred forty-seven patients were enrolled, and 88% had their tumors tested for at least one gene. EGFR mutation frequency was 22.1% in NSCLC, and erlotinib achieved a response rate of 60% (95% CI, 32.3% to 83.7%). KRAS mutation frequency was 24.9% in NSCLC, and selumetinib failed to achieve its primary end point, with a response rate of 11% (95% CI, 0% to 48%). Completion of accrual to all other arms was not feasible. In NSCLC, patients with EGFR mutations had the longest median survival (3.51 years; 95% CI, 2.89 to 5.5 years), followed by those with ALK rearrangements (2.94 years; 95% CI, 1.66 to 4.61 years), those with KRAS mutations (2.3 years; 95% CI, 2.3 to 2.17 years), those with other genetic abnormalities (2.17 years; 95% CI, 1.3 to 2.74 years), and those without an actionable mutation (1.85 years; 95% CI, 1.61 to 2.13 years). This basket trial design was not feasible for many of the arms with rare mutations, but it allowed the study of the genetics of less common malignancies.