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Comparative Effectiveness of Treatment Strategies For Multiple Myeloma in Elderly Patients: A Network Meta-Analysis
A710
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
of research results. Results: Oral fluoropyrimidine have shown similar efficacy to infusional 5-FU, with better safety profile. The most common toxicities were nausea, fatigue, diarrhoea, leukopenia, anaemia and neutropenia. 5-FU showed a higher incidence of grade 3/4 neutropenia. Non-hematological toxicities showed similar incidences in both treatment options. There was no statistically significant differences in survival between oral and infusional fluoropyrimidine. Besides, oral fluoropyrimidine does not require a central venous port or continuous intravenous infusion, decreasing complications and prolonging the interval between hospital visits. Conclusions: The obtained data show that oral fluoropyrimidine can be considered in patients with aCRC taken into account comparable efficacy, acceptable toxicity and feasibility. Oral administration of fluoropyrimidine is preferred infusion therapy, because it is associated with lower risk of complications and higher compliance. PCN11 Incidence and Risk Factors of Glucocorticoid-Induced Diabetes Mellitus in Lymphoma Patients Treated with GlucocorticoidContaining Chemotherapy Zhou KR1, Chu MH1, Lo KY1, Watanabe JH2 1The Chinese University of Hong Kong, Shatin, Hong Kong, 2University of California San Diego, La Jolla, CA, USA
Objectives: High dose glucocorticoid as a part of the treatment of non-Hodgkin’s lymphoma was found to induce diabetes in these patients. The present study aims to investigate the incidence and risk factors of glucocorticoid-induced diabetes mellitus (GDM) in Hong Kong. This study also aims to study the influence of GDM on the outcome and effect of chemotherapy on glycemic control. Methods: Patients without history of diabetes aged 18 or above with confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) treated with any steroid-containing chemotherapy with or without rituximab between 2009 and 2014 at the Prince of Wales Hospital, were analyzed retrospectively. GDM diagnosis was defined based on the definition of DM according to the American Diabetes Association (ADA). These include a fasting plasma glucose ≥ 7mmol/L or HbA1c ≥ 6.5%. Binary logistic regression was used to identify possible significant risk factors of GDM. Diabetic patients treated for DLBCL were also identified and their medications before and after chemotherapy were recorded. Self-reported side effects were also recorded. Results: Among the 78 patients included in the study, 5 developed GDM (6.4%). Steroid administration prior to glucocorticoid-containing chemotherapy was the only significant risk factor associated with GDM development by univariate analysis. Gender, old age, smoking history, overweight, hypertension, dyslipidemia, and pre-diabetes prior to chemotherapy were not found to be significantly associated with GDM development. None of the GDM patients received treatment for hyperglycemia. Two diabetic patients had changes in the original anti-diabetic medications and another 2 required the addition of insulin for glucose control. The most common glucocorticoid-related side effects reported were weight gain and nausea. Conclusions: The incidence of GDM was found to be 6.4%. Diabetic control may also be worsened in diabetic patients during chemotherapy. These patients may be considered to have more frequent plasma glucose monitoring during chemotherapy. PCN12 Baseline Characteristics and Survival of Patients Diagnosed with Advanced NSCLC in Sweden Between 2006 and 2013, Matched (1:4) To A Comparison Cohort From The General Population Linden S1, Banos Hernaez AM2, Redig J2, Justo N2, Nilsson J2, Montonen J1, Verpillat P1 1Boehringer Ingelheim, Ingelheim am Rhein, Germany, 2Mapi Group, Stockholm, Sweden
Objectives: Lung cancer is the most commonly diagnosed cancer in men and the third most common in women. However, detailed information on characteristics of patients with advanced non-small cell lung cancer (NSCLC) in routine clinical care, compared to the general population is limited. Methods: This non-interventional study is based on existing data from the population based national Swedish Cancer Registry. All Swedish adult patients diagnosed with advanced NSCLC between 2006 and 2013 were included and matched (1:4) by age at diagnosis, gender and region of residence to a sample from the general population. Results: 12,355 patients diagnosed with advanced NSCLC were included in the analysis and matched to 49,351 individuals. At the date of the initial NSCLC diagnosis, the mean age was 68.9 years (SD 9.8, range 22-99), the stage was IIIb in 19.1% (n= 2,364) or IV in 80.1% (n= 9,991), and 52% (n= 6,423) were male. Adenocarcinoma was the most frequent morphology (64.2%, n= 7,926) followed by squamous cell carcinomas (21.7%). Of the NSCLC cohort, 96.5% (n= 11,919) were deceased at the end of follow-up (May 2016). NSCLC patients had a median survival time of 6.3 months (quartile1 2.6, quartile3 13.7) since diagnosis. In contrast, of the general population cohort only 17.9% (n= 8,842) were deceased at the end of follow-up. Conclusions: As expected, NSCLC diagnosed patients have a relatively high mean age (69 years) and significant higher mortality was observed. With the vast majority of patients above 65 years, significant more comorbidities are expected, resulting in clinical and economic consequences. Therefore, we are linking this population with additional data to further analyse comorbidities at initial diagnosis and outcomes of interest during NSCLC treatment. PCN13 Efficacy of Palbociclib Combinations Versus Endocrine Therapies in Advanced/ Metastatic Breast Cancer: Network Meta-Analysis Chirila C1, Mitra D2, Colosia A1, Ling C3, Odom D1, Iyer S2, Kaye JA4 Health Solutions, Research Triangle Park, NC, USA, 2Pfizer, Inc., New York, NY, USA, 3RTI Health Solutions, Manchester, UK, 4RTI Health Solutions, Waltham, MA, USA
1RTI
Objectives: Palbociclib is a novel CDK4/6 inhibitor approved in the United States for HR+/ HER2- advanced/metastatic breast cancer (ABC/MBC) in combination with letrozole as initial endocrine-based therapy (first-line) in postmenopausal women, or with fulvestrant (second-line) in women with disease progression following endocrine therapy. However, limited data are available on the efficacy of palbociclib
combinations compared to other endocrine therapies. We compared progressionfree survival (PFS) hazard ratio (HR) of palbociclib combinations against first- and second-line endocrine therapies using a mixed-treatment comparison (MTC) metaanalysis of randomized, controlled trials (RCTs). Methods: A systematic literature review conducted by two independent reviewers identified relevant RCTs in ABC/ MBC. Separate networks were developed for palbociclib plus letrozole and palbociclib plus fulvestrant. MTC analyses were conducted using a Bayesian approach. Based on output from MTC, treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). Results: Sixty-four unique studies met inclusion criteria. Because of sparse networks, fixed-effects model results are reported. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all first-line comparators, with the following posterior median PFS HRs and 95% credible intervals (CrI): anastrozole 1 mg, 0.58 (0.42-0.83); and tamoxifen 20 or 40 mg, 0.41 (0.31-0.53). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and was associated with significantly longer PFS than the second-line comparators: anastrozole 1 mg, 0.37 (0.27-0.50); letrozole 2.5 mg, 0.36 (0.22-0.60); fulvestrant 250 mg, 0.36 (0.27-0.48); fulvestrant 500/250 mg, 0.41 (0.23-0.68); and exemestane 25 mg, 0.39 (0.23-0.64). There was no significant difference in the PFS HR for palbociclib plus fulvestrant compared to everolimus plus exemestane (1.03; 95%, 0.58-1.76). Conclusions: The MTC results suggest that palbociclib plus letrozole and palbociclib plus fulvestrant are associated with significantly improved PFS compared with all first-line and most second-line endocrine treatments for ABC/MBC. PCN14 Comparative Effectiveness of Treatment Strategies For Multiple Myeloma in Elderly Patients: A Network Meta-Analysis Buchberger M1, Rochau U2, Vukicevic D1, Willenbacher W3, Chaimani A4, Efthimiou O4, Siebert U5 1UMIT - University for Health Sciences, Medical Informatics and Technology, Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, Hall i.T., Austria, 2UMIT - University for Health Sciences, Medical Informatics and Technology, Institute of Public Health, Medical Decision Making and HTA, Department of Public Health, Health Services Research and HTA/ ONCOTYROL - Center for Personalized Medicine, Hall i.T./ Innsbruck, Austria, 3ONCOTYROL - Center for Personalized Cancer Medicine, Area Health Technology Assessment/ Internal Medicine V—Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria, 4University of Ioannina School of Medicine, Ioannina, Greece, 5Harvard Medical School, Institute for Technology Assessment & Department of Radiology, Hall i.T., Austria
Objectives: To examine the comparative effectiveness of different first-line strategies currently used for patients with multiple myeloma (MM) > 65 years who are ineligible for stem cell transplantation, for the outcomes overall survival (OS) and progression-free survival (PFS). Treatment alternatives include multidrug regimens combining 2-5 drugs of different classes: prednisone (P), high-dose dexamethasone (D), low-dose dexamethasone (d), thalidomide (T), lenalidomide (R), bortezomib (V), cyclophosphamide (C), and melphalan (M). Methods: We performed a systematic literature search in MEDLINE, Embase, Cochrane Library, and CRD databases. We used a random-effects network meta-analysis (NMA) to estimate pooled hazard ratios with 95% confidence intervals for all treatment comparisons and outcomes. We ranked treatments using cumulative ranking probabilities. Results: The NMA comprised thirteen randomized controlled trials including 5573 patients comparing eleven treatment strategies. Treatment with VMPT-VT showed a statistically significant OS benefit compared to MPR and MP regimens. VTD showed a significant survival benefit compared to MP. Regarding PFS, the VMPT-VT strategy was superior to most of the other treatments. The NMA showed significantly better PFS for MPR-R compared to CTD, Rd, MPR, MPT, and MP. Comparison of Rd-Rd against Rd, MPT, and MP showed a significant benefit of Rd-Rd. The analysis showed VTD, MPV, and MPT to be favorable compared to MP regarding PFS. Based on the cumulative ranking probabilities, VMPT-VT, VTD, and Rd-Rd might be more effective than other treatment strategies in terms of OS. With respect to PFS, VMPT-VT, MPR-R, and Rd-Rd might be more effective. Conclusions: The NMA suggests that VMPT-VT, Rd-Rd, MPR-R, and VTD are more effective in terms of OS and PFS than other multidrug regimens for the first-line treatment of elderly patients with MM. However, further research should be considered to provide information on toxicity, quality of life, and cost-effectiveness for the different therapy approaches to consider all trade-offs. PCN15 Effectiveness and Safety of Braf Inhibitors in The Treatment of Braf-Mutated Unresectable or Metastatic Melanoma: Real World Data García-Avello A, Vega-Coca MD, Abdel-kader-Martin L, Poyatos-Ruiz L, Flores-Moreno S Hopital Universitario Virgen del Rocío, SEVILLA, Spain
Objectives: To assess the effectiveness and safety of BRAF inhibitors (BRAFi), alone or in combination with MEK inhibitors (MEKi), in patients with BRAF-mutated unresectable/metastatic melanoma in routine clinical practice. Methods: A singlecenter, retrospective, observational study was carried out. Inclusion criteria: All patients treated with BRAFi ± MEKi until May 2016. Data collected: demografic data, BRAFi used (vemurafenib or dabrafenib), MEKi use, previous treatments, ECOG performance status, metastatic disease, number of metastases and adverse events. Progression free survival (PFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method. Results: 25 patients met the inclusion criteria. 76% were male, with a mean age of 60.5 (range: 39-81) years. ECOG performance status was ≤ 1 in 72% of cases. 100% of patients had metastatic (56% with multiple metastases). Dabrafenib was used in 56% of patients and vemurafenb in 44%. MEKi were added in 72% of cases. BRAFi were the first-line treatment in the majority of patients (72%). The mean treatment duration with dabrafenib and vemurafenib at the end of the follow-up period was 8 and 3.5 months, respectively. In patients treated with dabrafenib + trametinib median PFS and OS were 6 (95%CI: 3.11-8.89) and 23 (95%CI: 1.94-44.06) months, respectively. In patients treated with dabrafenib monotherapy
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
of research results. Results: Oral fluoropyrimidine have shown similar efficacy to infusional 5-FU, with better safety profile. The most common toxicities were nausea, fatigue, diarrhoea, leukopenia, anaemia and neutropenia. 5-FU showed a higher incidence of grade 3/4 neutropenia. Non-hematological toxicities showed similar incidences in both treatment options. There was no statistically significant differences in survival between oral and infusional fluoropyrimidine. Besides, oral fluoropyrimidine does not require a central venous port or continuous intravenous infusion, decreasing complications and prolonging the interval between hospital visits. Conclusions: The obtained data show that oral fluoropyrimidine can be considered in patients with aCRC taken into account comparable efficacy, acceptable toxicity and feasibility. Oral administration of fluoropyrimidine is preferred infusion therapy, because it is associated with lower risk of complications and higher compliance. PCN11 Incidence and Risk Factors of Glucocorticoid-Induced Diabetes Mellitus in Lymphoma Patients Treated with GlucocorticoidContaining Chemotherapy Zhou KR1, Chu MH1, Lo KY1, Watanabe JH2 1The Chinese University of Hong Kong, Shatin, Hong Kong, 2University of California San Diego, La Jolla, CA, USA
Objectives: High dose glucocorticoid as a part of the treatment of non-Hodgkin’s lymphoma was found to induce diabetes in these patients. The present study aims to investigate the incidence and risk factors of glucocorticoid-induced diabetes mellitus (GDM) in Hong Kong. This study also aims to study the influence of GDM on the outcome and effect of chemotherapy on glycemic control. Methods: Patients without history of diabetes aged 18 or above with confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) treated with any steroid-containing chemotherapy with or without rituximab between 2009 and 2014 at the Prince of Wales Hospital, were analyzed retrospectively. GDM diagnosis was defined based on the definition of DM according to the American Diabetes Association (ADA). These include a fasting plasma glucose ≥ 7mmol/L or HbA1c ≥ 6.5%. Binary logistic regression was used to identify possible significant risk factors of GDM. Diabetic patients treated for DLBCL were also identified and their medications before and after chemotherapy were recorded. Self-reported side effects were also recorded. Results: Among the 78 patients included in the study, 5 developed GDM (6.4%). Steroid administration prior to glucocorticoid-containing chemotherapy was the only significant risk factor associated with GDM development by univariate analysis. Gender, old age, smoking history, overweight, hypertension, dyslipidemia, and pre-diabetes prior to chemotherapy were not found to be significantly associated with GDM development. None of the GDM patients received treatment for hyperglycemia. Two diabetic patients had changes in the original anti-diabetic medications and another 2 required the addition of insulin for glucose control. The most common glucocorticoid-related side effects reported were weight gain and nausea. Conclusions: The incidence of GDM was found to be 6.4%. Diabetic control may also be worsened in diabetic patients during chemotherapy. These patients may be considered to have more frequent plasma glucose monitoring during chemotherapy. PCN12 Baseline Characteristics and Survival of Patients Diagnosed with Advanced NSCLC in Sweden Between 2006 and 2013, Matched (1:4) To A Comparison Cohort From The General Population Linden S1, Banos Hernaez AM2, Redig J2, Justo N2, Nilsson J2, Montonen J1, Verpillat P1 1Boehringer Ingelheim, Ingelheim am Rhein, Germany, 2Mapi Group, Stockholm, Sweden
Objectives: Lung cancer is the most commonly diagnosed cancer in men and the third most common in women. However, detailed information on characteristics of patients with advanced non-small cell lung cancer (NSCLC) in routine clinical care, compared to the general population is limited. Methods: This non-interventional study is based on existing data from the population based national Swedish Cancer Registry. All Swedish adult patients diagnosed with advanced NSCLC between 2006 and 2013 were included and matched (1:4) by age at diagnosis, gender and region of residence to a sample from the general population. Results: 12,355 patients diagnosed with advanced NSCLC were included in the analysis and matched to 49,351 individuals. At the date of the initial NSCLC diagnosis, the mean age was 68.9 years (SD 9.8, range 22-99), the stage was IIIb in 19.1% (n= 2,364) or IV in 80.1% (n= 9,991), and 52% (n= 6,423) were male. Adenocarcinoma was the most frequent morphology (64.2%, n= 7,926) followed by squamous cell carcinomas (21.7%). Of the NSCLC cohort, 96.5% (n= 11,919) were deceased at the end of follow-up (May 2016). NSCLC patients had a median survival time of 6.3 months (quartile1 2.6, quartile3 13.7) since diagnosis. In contrast, of the general population cohort only 17.9% (n= 8,842) were deceased at the end of follow-up. Conclusions: As expected, NSCLC diagnosed patients have a relatively high mean age (69 years) and significant higher mortality was observed. With the vast majority of patients above 65 years, significant more comorbidities are expected, resulting in clinical and economic consequences. Therefore, we are linking this population with additional data to further analyse comorbidities at initial diagnosis and outcomes of interest during NSCLC treatment. PCN13 Efficacy of Palbociclib Combinations Versus Endocrine Therapies in Advanced/ Metastatic Breast Cancer: Network Meta-Analysis Chirila C1, Mitra D2, Colosia A1, Ling C3, Odom D1, Iyer S2, Kaye JA4 Health Solutions, Research Triangle Park, NC, USA, 2Pfizer, Inc., New York, NY, USA, 3RTI Health Solutions, Manchester, UK, 4RTI Health Solutions, Waltham, MA, USA
1RTI
Objectives: Palbociclib is a novel CDK4/6 inhibitor approved in the United States for HR+/ HER2- advanced/metastatic breast cancer (ABC/MBC) in combination with letrozole as initial endocrine-based therapy (first-line) in postmenopausal women, or with fulvestrant (second-line) in women with disease progression following endocrine therapy. However, limited data are available on the efficacy of palbociclib
combinations compared to other endocrine therapies. We compared progressionfree survival (PFS) hazard ratio (HR) of palbociclib combinations against first- and second-line endocrine therapies using a mixed-treatment comparison (MTC) metaanalysis of randomized, controlled trials (RCTs). Methods: A systematic literature review conducted by two independent reviewers identified relevant RCTs in ABC/ MBC. Separate networks were developed for palbociclib plus letrozole and palbociclib plus fulvestrant. MTC analyses were conducted using a Bayesian approach. Based on output from MTC, treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). Results: Sixty-four unique studies met inclusion criteria. Because of sparse networks, fixed-effects model results are reported. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all first-line comparators, with the following posterior median PFS HRs and 95% credible intervals (CrI): anastrozole 1 mg, 0.58 (0.42-0.83); and tamoxifen 20 or 40 mg, 0.41 (0.31-0.53). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and was associated with significantly longer PFS than the second-line comparators: anastrozole 1 mg, 0.37 (0.27-0.50); letrozole 2.5 mg, 0.36 (0.22-0.60); fulvestrant 250 mg, 0.36 (0.27-0.48); fulvestrant 500/250 mg, 0.41 (0.23-0.68); and exemestane 25 mg, 0.39 (0.23-0.64). There was no significant difference in the PFS HR for palbociclib plus fulvestrant compared to everolimus plus exemestane (1.03; 95%, 0.58-1.76). Conclusions: The MTC results suggest that palbociclib plus letrozole and palbociclib plus fulvestrant are associated with significantly improved PFS compared with all first-line and most second-line endocrine treatments for ABC/MBC. PCN14 Comparative Effectiveness of Treatment Strategies For Multiple Myeloma in Elderly Patients: A Network Meta-Analysis Buchberger M1, Rochau U2, Vukicevic D1, Willenbacher W3, Chaimani A4, Efthimiou O4, Siebert U5 1UMIT - University for Health Sciences, Medical Informatics and Technology, Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, Hall i.T., Austria, 2UMIT - University for Health Sciences, Medical Informatics and Technology, Institute of Public Health, Medical Decision Making and HTA, Department of Public Health, Health Services Research and HTA/ ONCOTYROL - Center for Personalized Medicine, Hall i.T./ Innsbruck, Austria, 3ONCOTYROL - Center for Personalized Cancer Medicine, Area Health Technology Assessment/ Internal Medicine V—Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria, 4University of Ioannina School of Medicine, Ioannina, Greece, 5Harvard Medical School, Institute for Technology Assessment & Department of Radiology, Hall i.T., Austria
Objectives: To examine the comparative effectiveness of different first-line strategies currently used for patients with multiple myeloma (MM) > 65 years who are ineligible for stem cell transplantation, for the outcomes overall survival (OS) and progression-free survival (PFS). Treatment alternatives include multidrug regimens combining 2-5 drugs of different classes: prednisone (P), high-dose dexamethasone (D), low-dose dexamethasone (d), thalidomide (T), lenalidomide (R), bortezomib (V), cyclophosphamide (C), and melphalan (M). Methods: We performed a systematic literature search in MEDLINE, Embase, Cochrane Library, and CRD databases. We used a random-effects network meta-analysis (NMA) to estimate pooled hazard ratios with 95% confidence intervals for all treatment comparisons and outcomes. We ranked treatments using cumulative ranking probabilities. Results: The NMA comprised thirteen randomized controlled trials including 5573 patients comparing eleven treatment strategies. Treatment with VMPT-VT showed a statistically significant OS benefit compared to MPR and MP regimens. VTD showed a significant survival benefit compared to MP. Regarding PFS, the VMPT-VT strategy was superior to most of the other treatments. The NMA showed significantly better PFS for MPR-R compared to CTD, Rd, MPR, MPT, and MP. Comparison of Rd-Rd against Rd, MPT, and MP showed a significant benefit of Rd-Rd. The analysis showed VTD, MPV, and MPT to be favorable compared to MP regarding PFS. Based on the cumulative ranking probabilities, VMPT-VT, VTD, and Rd-Rd might be more effective than other treatment strategies in terms of OS. With respect to PFS, VMPT-VT, MPR-R, and Rd-Rd might be more effective. Conclusions: The NMA suggests that VMPT-VT, Rd-Rd, MPR-R, and VTD are more effective in terms of OS and PFS than other multidrug regimens for the first-line treatment of elderly patients with MM. However, further research should be considered to provide information on toxicity, quality of life, and cost-effectiveness for the different therapy approaches to consider all trade-offs. PCN15 Effectiveness and Safety of Braf Inhibitors in The Treatment of Braf-Mutated Unresectable or Metastatic Melanoma: Real World Data García-Avello A, Vega-Coca MD, Abdel-kader-Martin L, Poyatos-Ruiz L, Flores-Moreno S Hopital Universitario Virgen del Rocío, SEVILLA, Spain
Objectives: To assess the effectiveness and safety of BRAF inhibitors (BRAFi), alone or in combination with MEK inhibitors (MEKi), in patients with BRAF-mutated unresectable/metastatic melanoma in routine clinical practice. Methods: A singlecenter, retrospective, observational study was carried out. Inclusion criteria: All patients treated with BRAFi ± MEKi until May 2016. Data collected: demografic data, BRAFi used (vemurafenib or dabrafenib), MEKi use, previous treatments, ECOG performance status, metastatic disease, number of metastases and adverse events. Progression free survival (PFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method. Results: 25 patients met the inclusion criteria. 76% were male, with a mean age of 60.5 (range: 39-81) years. ECOG performance status was ≤ 1 in 72% of cases. 100% of patients had metastatic (56% with multiple metastases). Dabrafenib was used in 56% of patients and vemurafenb in 44%. MEKi were added in 72% of cases. BRAFi were the first-line treatment in the majority of patients (72%). The mean treatment duration with dabrafenib and vemurafenib at the end of the follow-up period was 8 and 3.5 months, respectively. In patients treated with dabrafenib + trametinib median PFS and OS were 6 (95%CI: 3.11-8.89) and 23 (95%CI: 1.94-44.06) months, respectively. In patients treated with dabrafenib monotherapy