A phase 2 study of first-line nivolumab in patients with locally advanced or metastatic cutaneous squamous-cell carcinoma.

BACKGROUND: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC). METHODS: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities. CONCLUSIONS: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.

The Effect of Intrathoracic Lesion Location on Initial Tyrosine Kinase Inhibitor Response in Advanced Oncogene-Addicted Non-Small Cell Lung Cancer: A Comparison Between RECIST 1.1 and a Novel Method of Response Assessment (MAX).

INTRODUCTION: Different subtypes of non-small cell lung cancer (NSCLC) are associated with different patterns of metastatic spread. Anatomic location of lesions in the chest may influence patterns of cancer growth and the shrinkage to therapy. Consequently, lesion location could affect apparent response rates per RECIST. We sought to explore this and develop, as needed, treatment response assessments less affected by the location. METHODS: Cases of advanced oncogene-addicted NSCLC (EGFR, ALK, and ROS1) with pre- and on-therapy imaging during initial targeted therapy were identified. Lesions located in the lung parenchyma, pleural space or intra-thoracic lymph nodes were identified and analyzed separately from each other by RECIST 1.1 (unidimensional measurements) and by a novel MAX methodology (bidimensional measurements) which takes the axis with the greatest absolute percentage change on therapy in each location as the representative measurement. RESULTS: Three hundred three patients with 446 unidimensional measured lesions were included for RECIST analysis. Two hundred forty nine patients with 386 bidimensional measured lesions were included for MAX analysis, as well as the analysis comparing RECIST and MAX. Intrathoracic location significantly impacted percentage shrinkage and the response rate per RECIST. The response rates for pleural, intra-parenchymal and nodal lesions were 34.1%, 49.6%, and 68.3%, respectively (P = .0002). The MAX methodology both increased the apparent treatment effect and made it consistent between intrathoracic locations. For pleural, parenchymal and nodal lesions, the MAX calculated response rate were 83.7%, 72.2%, and 75.4%, respectively (P-value = .24). CONCLUSION: Intrathoracic lesion location affects RECIST-based treatment effectiveness estimations. The MAX methodology neutralizes location effect when examining impact of treatment and should be explored further.

Nivolumab treatment beyond progressive disease in advanced non-small cell lung cancer.

PURPOSE: This study evaluated the efficacy and safety of nivolumab treatment beyond progressive disease (PD) in non-small cell lung cancer (NSCLC). PATIENTS/METHODS: Medical records of consecutive patients with advanced NSCLC who received nivolumab between December 2015 and December 2018 were reviewed. Clinical outcomes of three groups of eligible patients who received nivolumab as a second-line treatment after PD were compared based on Response Evaluation Criteria in Solid Tumors v1.1. We conducted subgroup analyses in patients with and without new lesions at first PD. RESULTS: Twenty-eight patients continued nivolumab treatment beyond PD (TBP). Post PD, 46 patients switched to other anti-cancer treatment (OAT), and 21 received no further anti-cancer treatment (NAT). There were no significant differences in overall survival (OS) or survival post progression (SPP) between TBP and OAT groups (OS: 15.6 vs. 13.4 months, P = .40, SPP: 12.2 vs. 9.3 months, P = .42). Subgroup analyses indicated that among patients without new lesions at first PD, SPP was longer in the TBP than in the OAT groups (12.6 vs. 9.3 months, P = .22, HR: 0.64; 95% CI 0.31‒1.31). The frequency of immune-related adverse events leading to discontinuation during nivolumab beyond PD was equivalent to that for pre-PD (10.7 vs. 12.6%). CONCLUSIONS: No significant benefits were associated with continuation of nivolumab for advanced NSCLC patients. Continuation of nivolumab beyond PD could be a more useful option in patients without new lesions at first PD. Treatment-related toxicities require attention during nivolumab treatment not only before PD but also beyond PD.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues.

Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma.

BACKGROUND: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. METHODS: We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan-Meier method and compared by the Log Rank test. RESULTS: Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039). CONCLUSION: Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies.

Electrochemotherapy in treatment of canine oral malignant melanoma and factors influencing treatment outcome.

Background Oral malignant melanoma is the most common, but aggressive oral cancer in dogs with poor prognosis. Electrochemotherapy (ECT) has therapeutic potential in such tumors as effective local treatment. Therefore, the aim of this prospective clinical study was to evaluate treatment effectiveness of ECT in as first line treatment for canine oral malignant melanoma, and search for factors influencing treatment outcome. Methods Sixty-seven canines with primary oral malignant melanoma, non-candidates for first-line therapy, were enrolled. All dogs received ECT and follow-up exams for the span of two years. Results Based on RECIST criteria, the objective response rate was 100%, 89.5%, 57.7%, and 36.4%, in stage I, II, III and IV, respectively. Only patients in stage I, II and III with partial or complete response improved their quality of life. The median time to progression was 11, 7, 4 and 4 months, and median survival time after the treatment was 16.5, 9.0, 7.5 and 4.5 months, for patients in stage I, II, III and IV, respectively. Significantly better was local response in stage I and II disease (p = 0.0013), without the bone involvement (p = 0.043) Conclusions Electrochemotherapy is effective local treatment of oral canine malignant melanoma when no alternative treatment is available. Better response is expected in stage I and II patients with tumors without bone involvement.

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer.

BACKGROUND: The purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients had HR+/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes. RESULTS: Eight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase). CONCLUSIONS: RT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR+ MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR+ MBC.

Efficacy and safety profile of vismodegib in a real-world setting cohort of patients with advanced basal cell carcinoma in Argentina.

INTRODUCTION AND OBJECTIVES: Vismodegib (Erivedge® ), a hedgehog pathway inhibitor, is approved to treat metastatic or locally advanced basal cell carcinoma (BCC) not suitable for surgery or radiotherapy. Our main objectives were to study the objective response rate (ORR) assessed by treating physicians and safety of vismodegib in a real-world practice setting in Argentina. MATERIAL AND METHODS: This is a prospective cohort study in real-world practice. We included consecutive adult patients treated in Argentina with locally advanced or metastatic BCC not suitable for surgery or radiotherapy. Patients were followed until the end of the study, death, or loss to follow-up, whichever occurred first. Patients received 150 mg vismodegib PO daily. RESULT: We included in the analysis 63 patients who received treatment. Locally advanced BCC was present in 57 (90.4%) and metastatic disease in two (3.2%). ORR was observed in 46 patients (73%; 95% CI: 60.3-83.4), with partial response in 36 (57%; 95% CI: 44-69.5) and complete response in 10 (16%; 95% CI: 7.8-27.2). As to safety, 48 (76.2%) patients had at least one adverse event (AE). The most frequently observed AEs were muscular spasms in 25 (39.6%); dysgeusia in 23 (36.5%); alopecia in nine (14.2%); weight loss in seven (11.1%); and ageusia in (9.5%) patients. Serious AEs were observed in 11 (17%) patients with one episode of deep vein thrombosis and pulmonary embolism resulting in death. CONCLUSION: Our study provides additional evidence of the efficacy and tolerability of vismodegib in patients with locally advanced or metastatic BCC in a real-world practice.

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Consensus on the use of immune-related response criteria to evaluate the efficacy of immunotherapy in non-small cell lung cancer.

INTRODUCTION: Many methods used to assess the effectiveness of immune checkpoint (programmed death-ligand 1 or cytotoxic T-lymphocyte-associated protein 4) inhibitors for non-small cell lung cancer (NSCLC) are insufficient, as the therapeutic benefit of these agents is often underestimated. Consequently, immune-related evaluation criteria have been developed to better reflect their efficacy. The aim of this consensus was to obtain the opinion of lung cancer experts on the adequacy of immune-response criteria for evaluating the efficacy of these treatments. METHODS: Through two rounds of a modified Delphi consensus, 18 Spanish lung cancer experts participated in a 15-item questionnaire regarding the use of immunotherapies for NSCLC and the assessment criteria used to evaluate their effectiveness. RESULTS: Consensus was achieved on 80% of the items in the questionnaire. The panelists agreed that although the Response Evaluation Criteria in Solid Tumors (RECIST) are standard for the evaluation of solid tumors, immune-related response criteria would be useful for measuring the efficacy of immunotherapy. In addition, they considered that an overall survival (OS) rate at 2-5 years is the most useful end point for assessing the benefit of immunotherapy, as clinical benefit may extend beyond the RECIST criteria-defined progression of disease. CONCLUSIONS: Although immune-related response criteria have been developed to better evaluate the efficacy of immunotherapy, their use has not been validated and is restricted to investigational applications. However, they may prove to be a useful tool for measuring the efficacy of immunotherapy agents in NSCLC, especially the OS rate at 2-5 years.

Ressonância magnética com difusão na avaliação de pacientes com melanoma de coroide submetidos a braquiterapia / Diffusion-weighted magnetic resonance imaging in the evaluation of patients with choroidal melanoma submitted to brachytherapy

O melanoma de coroide é o tumor intraocular primário mais comum em adultos. Por possibilitar a conservação do globo ocular, a braquiterapia tem sido uma opção terapêutica nestes casos. Atualmente, o método de imagem mais utilizado para avaliação deste tumor é a ultrassonografia ocular, auxiliando na estimativa do tamanho e localização da lesão para controle e planejamento do tratamento. No entanto, a redução nas dimensões do tumor só é observada tardiamente após o tratamento. O objetivo deste trabalho é avaliar o papel da ressonância magnética (RM) com difusão na avaliação de pacientes com melanoma de coroide, no momento do diagnóstico e na avaliação de resposta terapêutica após braquiterapia. Foi realizado um estudo prospectivo, unicêntrico, aprovado pelo Comitê de Ética em Pesquisa, que incluiu pacientes com melanoma de coroide e indicação para braquiterapia. Foram propostos três exames de RM para cada paciente, sendo um antes e dois após o tratamento. Foi realizado cálculo do valor do coeficiente de difusão aparente (ADC) nos exames de RM e comparado com o controle tumoral local avaliado pelo acompanhamento oftalmológico (mapeamento de retina e ultrassonografia ocular). No período de 07/2018 a 06/2019, 19 pacientes foram incluídos, dos quais 13 realizaram exames de acompanhamento. A idade variou de 24 a 78 anos e 52,9% eram do sexo masculino. Na ultrassonografia ocular, a espessura e diâmetro médio dos tumores foi de 6,3 mm e 11,5 mm, respectivamente. Na RM inicial, a maioria dos tumores apresentava sinal alto ou intermediário em T1 (82,3%) e baixo em T2 (70,6%). Dois pacientes (15,4%) apresentaram sinais de progressão do tumor durante o acompanhamento e foi observada redução significativa nos valores de ADC médio entre a RM antes e após o tratamento nestes casos (p=0,02). Em conclusão, a RM com difusão demonstrou ser útil na avaliação de pacientes com melanoma de coroide e os valores de ADC médio podem ser utilizados para avaliação de resposta, permitindo identificar precocemente os pacientes com risco de progressão após a braquiterapia

Choroidal melanoma is the most common primary intraocular tumor in adults. Brachytherapy has been a therapeutic option in these cases because it allows the conservation of the eyeball. Currently, the most used imaging method for the evaluation of this tumor is ocular ultrasonography, helping to estimate the size and location of the lesion for treatment planning and follow-up. However, the reduction in tumor size is only observed late after treatment. The aim of this study is to evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of patients with choroidal melanoma at the time of diagnosis and in the evaluation of therapeutic response after brachytherapy. A prospective, unicentric study approved by the Research Ethics Committee, which included patients with choroidal melanoma and indication for brachytherapy, was performed. Three DW-MRI examinations were proposed for each patient, one before and two after treatment. The apparent diffusion coefficient (ADC) value was calculated on DW-MRI and compared with local tumor control assessed by ophthalmologic follow-up (retinal mapping and ocular ultrasound). From 07/2018 to 06/2019, 19 patients were included, of which 13 underwent follow-up examinations. Patients' age ranged from 24 to 78 years and 52.9% were male. At ocular ultrasound, the mean tumor thickness and diameter were 6.3 mm and 11.5 mm, respectively. At initial MRI, most tumors presented high or intermediate signal at T1 (82.3%) and low signal at T2 (70.6%). Two patients (15.4%) showed signs of tumor progression during follow-up and a significant reduction in mean ADC values was observed between MR before and after treatment in these cases (p = 0.02). In conclusion, DW-MRI has shown to be useful in assessing patients with choroidal melanoma and mean ADC values can be used for response assessment, allowing early identification of patients at risk for progression after brachytherapy

Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed. OBJECTIVE: The aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary. METHOD: A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated. RESULTS: A total of 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities and concerns with the heterogeneity of the studies. CONCLUSION: The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered.

Treatment-related changes in glioblastoma: a review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis.

The assessment of response to therapy in glioblastoma remains a challenge, because the surrogate measures of survival are subject to radiographic misinterpretation. A solid and reliable definition of progression is needed for both clinical decision-making and for evaluating response within the clinical trials. Historically, assessment criteria have used radiologic and clinical features aimed to correctly classify patients into progressive or non-progressive disease. The widely used RANO criteria are a valuable tool in disease evaluation, both in the clinical setting and in the clinical trials. However, assessment criteria have certain limitations that emerging image techniques have tried to overcome. Differentiating true progression from treatment-related changes (like pseudoprogression or pseudoresponse) is crucial in order not to prematurely discontinue adjuvant chemotherapy or redirect the patient to second-line options. This fact underscores the need for advanced radiologic techniques, like specific diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to play a role in distinguishing these phenomena.

Immunotherapy in prostate cancer: review of the current evidence.

Prostate cancer is the most common male malignancy in the Western world. Once it metastasizes, it is incurable. The current gold standard for metastatic disease is the combined docetaxel/prednisone regimen. Prostate cancer shows several characteristics that make it a suitable candidate for immunotherapy, as recently exemplified by the approval of sipuleucel-T, the first vaccine to treat any malignancy. Here, we review different tumor-associated antigen immunotherapy strategies currently being investigated, from a humanized radiolabeled monoclonal antibody (J-591) that targets radiation into tumor cells, moving on to vaccines and through to immunomodulator agents such as anti-CPLA-4 and anti-PD-1 monoclonal antibodies that activate T-cell responses via immune checkpoint inhibition. We explore different opinions on the best approach to integrate immunotherapy into existing standard therapies, such as androgen-deprivation therapy, radiotherapy or chemotherapy, and review different combination sequences, patient types and time points during the course of the disease to achieve a lasting immune response. We present data from recent phase III clinical trials that call for a change in trial endpoint design with immunotherapy agents, from the traditional tumor progression to overall survival and how such trials should include immune response measurements as secondary or intermediate endpoints to help identify patient clinical benefit in the earlier phases of treatment. Finally, we join in the recent questioning on the validity of RECIST criteria to measure response to immunotherapeutic agents, as initial increases in the size of tumors/lymph nodes, which are part of a normal immune response, could be categorized as disease progression under RECIST.

Response to sorafenib treatment in advanced metastatic thyroid cancer.

OBJECTIVE: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma. SUBJECTS AND METHODS: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration was 12 ± 3 months (range 6-16 months). RESULTS: Eight patients were included (seven papillary, one insular variant). The eight patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. One patient showed a partial response with tumor regression of -35%, six months after the beginning of the treatment; five patients exhibited stable disease and two patients had progressive disease and died. Thyroglobulin decreased within 4 weeks in all patients by 50% ± 23%. Adverse events: one patient had heart failure, and recovered after sorafenib withdrawal. However, she died five months later of sudden death. CONCLUSION: These data suggest a possible role for sorafenib in the treatment of progressive metastatic DTC. Adverse event are usually manageable, but severe ones may appear and these patients should be strictly controlled.

Response to sorafenib treatment in advanced metastatic thyroid cancer / Resposta ao tratamento com sorafenibe em pacientes com carcinoma metastático de tireoide

Objective: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma.Subjects and methods: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration was 12 ± 3 months (range 6-16 months).Results: Eight patients were included (seven papillary, one insular variant). The eight patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. One patient showed a partial response with tumor regression of -35%, six months after the beginning of the treatment; five patients exhibited stable disease and two patients had progressive disease and died. Thyroglobulin decreased within 4 weeks in all patients by 50% ± 23%.Adverse events: one patient had heart failure, and recovered after sorafenib withdrawal. However, she died five months later of sudden death.Conclusion: These data suggest a possible role for sorafenib in the treatment of progressive metastatic DTC. Adverse event are usually manageable, but severe ones may appear and these patients should be strictly controlled.

Objetivo: Investigar a eficácia do sorafenibe no carcinoma de tireoide metastático progressivo e refratário à iodoterapia.Sujeitos e métodos: Estudo observacional do efeito do sorafenibe off-label administrado 400 mg duas vezes ao dia. A duração da terapia foi de 12 ± 3 meses (variação de 6-16 meses).Resultados: Oito pacientes foram incluídos (sete com variante papilífera e um com variante insular). Os oito pacientes que preencheram os critérios do estudo receberam o sorafenibe 400 mg por via oral duas vezes por dia até progressão da doença ou toxicidade inaceitável. Um paciente apresentou uma resposta parcial com regressão tumoral da lesão alvo de 35% seis meses após o início do tratamento; cinco pacientes apresentaram doença estável e dois pacientes progrediram e morreram. A tireoglobulina diminuiu 50% ± 23% em 4 semanas em todos os pacientes.Eventos adversos: um paciente teve insuficiência cardíaca e morreu por morte súbita cinco meses após a retirada do sorafenibe.Conclusão: Esses dados sugerem um possível papel para sorafenibe para o tratamento do CDT metastático progressivo.