Drugs Xagena
The ASCO Task Force has applied the Framework to four clinical scenarios in which multiple trials have compared new treatment options with current standards of care: first-line treatment for metastatic non-small-cell lung cancer, treatment of advanced multiple myeloma, treatment of metastatic castration-resistant prostate cancer, and adjuvant therapy for women with human epidermal growth factor receptor 2-positive breast cancer.
These scenarios were selected to demonstrate the potential utility of the approach for diverse clinical circumstances and to inform refinements to the framework.
Metastatic non-small-cell lung cancer
Clinical benefit, toxicity, net health benefit ( NHB ), and cost of four regimens were compared with standard-of-care regimen used in clinical trials for first-line treatment of metastatic non-small-cell lung cancer: (A) Bevacizumab, Paclitaxel, and Carboplatin versus Carboplatin plus Paclitaxel ( control ) [ N Engl J Med 2006; 355:2542–2550 ]; (B) Cisplatin plus Pemetrexed versus Cisplatin plus Gemcitabine ( control ) [ J Clin Oncol 2008; 26:3543–3551 ]; (C) Docetaxel plus Gemcitabine versus Docetaxel plus Cisplatin ( control ) [ Lancet 2001; 357:1478–1484 ]; and (D) Erlotinib versus Cisplatin plus Docetaxel or Cisplatin plus Gemcitabine ( control ) in patients with EGFR mutation–positive advanced NSCLC [ Lancet Oncol 2012; 13:239–246 ].
The costs were based on average sales price as of October 2014 for intravenous therapies and on information from UnitedHealthcare for oral drugs; shown per month of treatment.
(A) Bevacizumab, Paclitaxel, and Carboplatin has overall survival ( OS ) of 12.3 months versus 10.3-month for Carboplatin plus Paclitaxel ( control ), 15 grade 3 to 5 toxicities versus 22 for control, NHB of 16 of maximum 130, and cost of $11,907.87 per month versus $182.09 per month for control.
(B) Cisplatin plus Pemetrexed has overall survival of 10.3 months versus 10.3-month for Cisplatin plus Gemcitabine ( control ), 10 grade 3 to 5 toxicities versus 10 for control, NHB of zero of maximum 130, and cost of $9,193.07 per month versus $811.72 per month for control.
Clinical benefit, toxicity, net health benefit ( NHB ), and cost using Cisplatin / Pemetrexed versus Cisplatin / Gemcitabine ( control ) for first-line treatment of metastatic non–small-cell lung cancer in patients with nonsquamous histology. Raw data for each parameter are shown above each bar.
Cost is based on average sales price as of October 2014 for intravenous therapies and on information from UnitedHealthcare for oral drugs4; shown per month of treatment.
Cisplatin / Pemetrexed has an overall survival of 11.8 months versus 10.4 months for Cisplatin / Gemcitabine ( control ), 10 grade 3 to 5 toxicities versus 10 for control, NHB of 16 of a maximum of 130, and cost of $9,193.07/month versus $811.72/month for control.
(C) Docetaxel plus Gemcitabine has overall survival of 9.5 months versus 10.0-month for Docetaxel plus Cisplatin ( control ), 13 grade 3 to 5 toxicities versus 15 for control, NHB of zero of maximum 130, and cost of $2,184.18 per month versus $2,019.80 per month for control.
(D) Oral Erlotinib has median progression-free survival ( PFS ) of 9.7 months versus 5.2 months for Cisplatin plus Docetaxel or Cisplatin plus Gemcitabine ( control ), eight grade 3 to 5 toxicities versus 12 for control, NHB of 44 of maximum 130, and cost of $4,607.63 per month versus $1,686.99 per month for Cisplatin plus Docetaxel and $903.31 per month for Cisplatin plus Gemcitabine.
Advanced multiple myeloma
Clinical benefit, toxicity, net health benefit, and cost of Bortezomib, Melphalan, and Prednisone were compared with Melphalan plus Prednisone ( control ) in clinical trial for first-line treatment of advanced multiple myeloma [ N Engl J Med 2008; 359:906–917 ] [ J Clin Oncol 2013; 31:448–455 ].
Costs were based on average sales price as of October 2014 for intravenous therapies and on information from UnitedHealthcare for oral drugs; shown per month of treatment .
Bortezomib, Melphalan, and Prednisone has overall survival of 56.4 months versus 43.1-month for Melphalan plus Prednisone ( control ), 42 grade 3 to 5 toxicities versus 34 for control, NHB of 47 of maximum 130, and cost of $7,042.70 per month versus $279.45 per month for control.
Metastatic castration-resistant prostate cancer
Clinical benefit, toxicity, net health benefit, and cost of three regimens were compared with standard-of-care regimen used in clinical trial for first-line treatment of metastatic castration-resistant prostate cancer: (A) Abiraterone plus Prednisone versus placebo ( control ) [ N Engl J Med 2011; 364:1995–2005 ] [ Lancet Oncol 2012; 13:1210–1217 ] (B) Cabazitaxel plus Prednisone versus Mitoxantrone plus Prednisone ( control ) [ Lancet 2010; 376:1147–1154 ] and (C) Enzalutamide versus placebo ( control ) [ N Engl J Med 2012; 367:1187–1197 ].
Costs were based on average sales price as of October 2014 for intravenous therapies and on information from UnitedHealthcare for oral drugs; shown per month of treatment.
(A) Abiraterone plus Prednisone has overall survival of 14.8 months versus 10.9-month for placebo ( control ), 37 grade 3 to 5 toxicities versus 34 for control, NHB of 42 of maximum 130, and cost of $7,523.88 per month versus $0 per month for control.
(B) Cabazitaxel plus Prednisone has overall survival of 15.1 months versus 12.7 months for Mitoxantrone plus Prednisone ( control ), 21 grade 3 to 5 toxicities versus 19 for control, NHB of 16 of maximum 130, and cost of $10,699.43 per month versus $245.14 per month for control.
(C) Enzalutamide has overall survival of 18.4 months versus 13.6 months for placebo ( control ), eight grade 3 to 5 toxicities versus six for control, NHB of 32 of maximum 130, and cost of $8,494.91 per month versus $0 per month for control.
Human EGFR2-positive breast cancer
Clinical benefit, toxicity, net health benefit, and cost of two regimens were compared with standard-of-care regimen used in clinical trial for adjuvant treatment of human epidermal growth factor receptor 2–positive breast cancer: (A) Doxorubicin plus Cyclophosphamide followed by Paclitaxel plus Trastuzumab and total of 1 year of Trastuzumab versus Doxorubicin, Cyclophosphamide, and Paclitaxel ( control ) [ N Engl J Med 2005; 353:1673–1684 ] [ J Clin Oncol 2011; 29:3366–3373 ] and (B) Doxorubicin, Docetaxel, Carboplatin, and Trastuzumab followed by total of 1 year of Trastuzumab versus Doxorubicin, Cyclophosphamide, and Docetaxel ( control ) [ N Engl J Med 2011; 365:1273–1283 ].
Costs were based on average sales price as of October 2014 for intravenous therapies and on information from UnitedHealthcare for oral drugs; shown as cost of delivering entire course of regimen.
(A) Doxorubicin, Cyclophosphamide, and Paclitaxel plus Trastuzumab versus Doxorubicin, Cyclophosphamide, and Paclitaxel ( control ) is linked to hazard ratio ( HR ) of 0.61, or 39% reduction in risk of death, when compared with control, three grade 3 to 5 toxicities versus three for control; NHB of 48 of maximum 100, and cost of $73,165.62 versus $3,405.02 for control.
(B) Doxorubicin, Docetaxel, Carboplatin, and Trastuzumab versus Doxorubicin, Cyclophosphamide, and Docetaxel ( control ) is associated with hazard ratio of 0.77, or 23% reduction in risk of death, when compared with control, 20 grade 3 to 5 toxicities versus 20 for control, NHB of 32 of maximum 100, and cost of $65,707.59 versus $7,052.94 for control. ( Xagena )
Schnipper LE et al, J Clin Oncol 2015; Published online before print
XagenaMedicine_2015
