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INTRODUCTION: While no direct comparative data exist for crizotinib in ROS1+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent. The objective of this study was to assess the cost-effectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC. METHODS: A Markov model was developed with a 10-year time horizon from the perspective of the Canadian publicly-funded health care system. Health states included progression-free survival (PFS), up to two further lines of therapy post-progression, palliation and death. Given a lack of comparative data and small study samples, crizotinib or chemotherapy studies with advanced ROS1+ NSCLC patients were identified and time-to-event data from digitized Kaplan-Meier curves were collected to pool PFS data. Costs of drugs, treatment administration, monitoring, adverse events and palliative care were included in 2018 Canadian dollars, with 1.5% discounting. An incremental cost-effectiveness ratio (ICER) was estimated probabilistically using 5000 simulations. RESULTS: In the base-case probabilistic analysis, crizotinib produced additional 0.885 life-years and 0.772 quality-adjusted life-years (QALYs) at an incremental cost of $238,077, producing an ICER of $273,286/QALY gained. No simulations were found to be cost-effective at a willingness-to-pay threshold of $100,000/QALY gained. A scenario analysis assuming efficacy equivalent to the ALK+ NSCLC population showed a slightly more favorable cost-effectiveness profile for crizotinib. CONCLUSIONS: Available data appear to support superior activity of crizotinib compared to chemotherapy in ROS1+ advanced NSCLC. At the list price, crizotinib was not cost-effective at commonly accepted willingness-to-pay thresholds across a wide range of sensitivity analyses.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Anos de Vida Ajustados por Qualidade de Vida , Antineoplásicos/economia , Canadá , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Custo-Benefício , Crizotinibe/economia , Rearranjo Gênico , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Cadeias de Markov , Terapia de Alvo Molecular/economia , Terapia de Alvo Molecular/métodos , Intervalo Livre de ProgressãoRESUMO
Renal cell carcinoma accounts for a significant proportion of cancer diagnoses in Canadians. Over the past several years, the management of renal cell cancers has undergone rapid changes in all prognostic risk categories, resulting in improved oncologic outcomes. Novel strategies for metastatic disease make use of the synergy between checkpoints and angiogenesis inhibition. Moreover, combination checkpoint inhibition has demonstrated durable efficacy in some patients. Adjuvant immunotherapy has recently shown a survival benefit for the first time in select cases. Significant efforts are underway to explore new compounds or combinations for later-line diseases, such as inhibitors of hypoxia-inducible factors and radiolabeled biomolecules targeting tumor antigens within the neoplastic microenvironment for precise payload delivery. In this manuscript, we provide a comprehensive review of the available data addressing key therapeutic areas pertaining to systemic therapy for metastatic and localized disease, review the most relevant prognostic tools, describe local therapies and management of CNS disease, and discuss practice-changing trials currently underway. Finally, we focus on some of the practical aspects for general practitioners in oncology caring for patients with renal cell carcinoma.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Clínicos Gerais , Oncologia/métodosRESUMO
Extragonadal germ cell tumors (EGCTs) are uncommon, and those involving the prostate are rare. We report on a primary seminoma of the prostate in a 56-year-old male presenting with scrotal pain, urinary frequency and urgency, and erectile dysfunction. Digital rectal examination revealed a hard, markedly enlarged prostate projecting posteriorly into the rectum. All 12 cores from ultrasound-guided prostate biopsy revealed malignant cells that stained positive for OCT4, PLAP, and CD117. Imaging revealed a 10.2 cm x 7.8 cm x 8.4 cm prostate mass with irregular nodular margins extending superiorly to the base of the bladder and posteriorly abutting the anterior rectal wall. There was no evidence of distant metastatic disease on both nuclear medicine and CT scans of the chest, abdomen, and pelvis. An 11 mm right internal iliac lymph node and several tiny sub-centimeter external iliac nodes were noted bilaterally. The patient was treated with radiotherapy to the prostate and pelvic lymph nodes. The pelvic lymph nodes were treated with 20 Gy in eight fractions, followed by a boost to the prostate for a further 20 Gy in eight fractions. There was a significant response during treatment that allowed an adaptive boost for a further 10 Gy in four fractions to bring the total dose to the prostate to 50 Gy in 20 fractions. Treatment was well tolerated. Adjuvant chemotherapy was not recommended. He remains disease-free 24 months post-treatment. This case report indicates that like most seminomas, extragonadal seminomas are exquisitely sensitive to radiotherapy and may be considered for the primary treatment of non-metastatic disease. To our knowledge, this is the first reported case of the sole use of radiotherapy to treat a primary seminoma of the prostate.
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INTRODUCTION: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel. METHODS: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response. RESULTS: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response, or primary PSA progression. CONCLUSIONS: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.
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BACKGROUND: Health care policies, including drug-funding policies, influence physician practice. Funding policies are especially important in the area of cancer care since cancer is a leading cause of death that is responsible for a significant level of health care expenditures. Recognizing the rising cost of cancer therapies, Cancer Care Ontario (CCO) established a funding process to provide access to new, effective agents through a "New Drug Funding Program" (NDFP). The purpose of this study is to describe oncologists' perceptions of the impact of NDFP priority setting decisions on their practice. METHODS: This is a qualitative study involving semi-structured, in-depth interviews with 46 medical oncologists in Ontario. Oncologists were asked to describe the impact of CCO's NDFP drug funding decisions on their practice. Analysis of interview transcripts commenced with data collection. RESULTS: Our key finding is that many of the medical oncologists who participated in this study did not accept limits when policy decisions limit access to cancer drugs they feel would benefit their patients. Moreover, overcoming those limits had a significant impact on oncologists' practice in terms of how they spend their time and energy and their relationship with patients. CONCLUSION: When priority setting decisions limit access to cancer medications, many oncologists' efforts to overcome those limits have a significant impact on their practice. Policy makers need to seriously consider the implications of their decisions on physicians, who may go to considerable effort to circumvent their policies in the name of patient advocacy.
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Antineoplásicos/economia , Atitude do Pessoal de Saúde , Política de Saúde , Prioridades em Saúde/legislação & jurisprudência , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência , Oncologia/tendências , Neoplasias/tratamento farmacológico , Relações Médico-Paciente , Autonomia Profissional , Antineoplásicos/provisão & distribuição , Tomada de Decisões , Aprovação de Drogas/economia , Aprovação de Drogas/legislação & jurisprudência , Feminino , Humanos , Entrevistas como Assunto , Masculino , Oncologia/economia , Ontário , Defesa do Paciente , Administração da Prática Médica , Pesquisa QualitativaRESUMO
INTRODUCTION: In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiraterone use was obtained and its impact on clinical parameters was examined. METHODS: Sixty-one patients from nine Canadian centres were enrolled, with prior abiraterone use known for 60 patients. Prostate-specific antigen (PSA) response rate, safety, and impact on QoL life were analyzed as a function of prior abiraterone use. RESULTS: Overall, 92% of patients were ECOG 0/1, 88% had bone metastases, and 25% visceral metastases. Patients treated without prior abiraterone (NoPriorAbi) (n=35, 58%) and with prior abiraterone (PriorAbi) (n=25, 42%) had similar baseline characteristics, except for age and prior cumulative docetaxel dose. Median number of cabazitaxel cycles received was similar between groups (NoPriorAbi=6, PriorAbi=7), as was PSA response rate (NoPriorAbi=36.4%, PriorAbi=45.0%, p=0.54). Almost one-third (31%) of patients received prophylactic granulocyte colony-stimulating factors. Most frequent Grade 3/4 toxicities were neutropenia (14.8%); anemia, febrile neutropenia, fatigue (each at 9.8%); and diarrhea (8.2%). No treatment-related adverse event leading to death was observed. QoL and pain were improved with no difference seen between groups. Treatment discontinuation was mainly due to disease progression (45.9%) and adverse events (32.8%). CONCLUSIONS: In routine clinical practice, cabazitaxel's risk-benefit ratio in mCRPC patients previously treated with docetaxel seems to be maintained independent of prior abiraterone use.