Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Randomized Controlled Trial Comparative Study
HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma.
Purpose Metastatic pancreatic ductal adenocarcinoma is characterized by excessive hyaluronan (HA) accumulation in the tumor microenvironment, elevating interstitial pressure and impairing perfusion. Preclinical studies demonstrated pegvorhyaluronidase alfa (PEGPH20) degrades HA, thereby increasing drug delivery. Patients and Methods Patients with previously untreated metastatic pancreatic ductal adenocarcinoma were randomly assigned to treatment with PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) or nab-paclitaxel/gemcitabine (AG). ⋯ Conclusion This study met its primary end points of PFS and TE event rate. The largest improvement in PFS was observed in patients with HA-high tumors who received PAG. A similar TE event rate was observed between the treatment groups in stage 2 of the trial.
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Purpose Cancer drug prices at launch have increased in recent years. It is unclear how individual drug prices change over time after launch and what market determinants influence these changes. We measured the price trajectories of a cohort of cancer drugs after their launch into the US market and assessed the influence of market structure on price changes. ⋯ Conclusion Anticancer drug costs may change substantially after launch. Regardless of competition or supplemental indications, there is a steady increase in costs of patented anticancer agents over time. New regulations may be needed to prevent additional increases in drug costs after launch.
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Randomized Controlled Trial Multicenter Study Comparative Study
Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial.
Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome-positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). ⋯ Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.
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Multicenter Study
Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma.
Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. ⋯ Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.
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Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. ⋯ Although a subset of sarcomas appears inflamed and responsive to immune checkpoint blockade with programmed death 1 (PD-1) targeted agents, novel immunotherapies and combinations likely will be needed for most subtypes. A variety of approaches-including targeting immune checkpoints other than PD-1; modulating tumor-associated macrophage phenotype from tumor-promoting to tumor-suppressive status; using cellular-based therapies, such as chimeric antigen and high-affinity T-cell receptors to deepen the adaptive immune response; and reinvigorating older approaches, such as vaccines and oncolytic virus-based treatments-are being investigated. The goal of these new approaches is to harness subtype-specific insights into cancer and immune biology to bring more effective and less toxic treatments to the clinic for the benefit of patients with sarcoma.