Adjuvant dabrafenib and trametinib for patients with resected BRAF -mutated melanoma: DESCRIBE-AD real-world retrospective observational study.

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF - V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF -mutated melanoma patients aged ≥18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Teleoncology: A Solution for Everyone? A Single-Center Experience with Telemedicine during the Coronavirus Disease 2019 (COVID-19) Pandemic.

Since the beginning of the COVID-19 pandemic, the use of telehealth was rapidly implemented without previous evidence. The ONCOTELEMD study aimed to evaluate the opinion of patients attended via telemedicine during this period and to study factors that condition patient preferences on its use. Included patients had a confirmed cancer diagnosis and were contacted by telephone between 13 March and 30 April 2020, in the Medical Oncology Service of Hospital Parc Taulí, Sabadell. A 12-question survey was presented to them between 4 February and 19 April 2021. Statistical analysis was carried out using chi-square and multivariable logistic regression tests. Six hundred forty-six patients were included; 487 responded to the survey. The median age was 68 years (27-90), 55.2% were female. Most patients had a surveillance visit (65.3%) and were diagnosed with colorectal or breast cancer (43% and 26.5%, respectively); 91.8% of patients were satisfied, and 60% would accept the use of telemedicine beyond the pandemic. Patients aged more than 50 years (OR 0.40; 95% CI, 0.19-0.81; p = 0.01) and diagnosed with breast cancer (OR 0.45; 95% CI, 0.26-0.69; p < 0.001) were less predisposed to adopt telehealth in the future. Patients agreed to be informed via telehealth of scan or lab results (62% and 84%, respectively) but not of new oral or endovenous treatments (52% and 33.5%, respectively). Additionally, 75% of patients had a medium or low-null technologic ability, and 51.3% would only use the telephone or video call to contact health professionals. However, differences were found according to age groups (p < 0.0001). In total, patients surveyed were satisfied with telemedicine and believed telehealth could have a role following the COVID-19 pandemic. Moreover, our results remark on the importance of individualizing the use of telehealth, showing relevant data on patient preferences and digital literacy.

Immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies, in a patient with melanoma treated with BRAF/MEK inhibitors.

The effect of serine/threonine-protein kinase B-Raf/mitogen-activated protein kinase (BRAF/MEK) inhibitors on the immune system is not clearly described, but rare cases of autoimmune phenomena have been reported. The clinical case we present below is the first report of a necrotizing myopathy related to dabrafenib/trametinib treatment. A 48-year-old man started dabrafenib/trametinib for stage IV BRAF-V600E mutated cutaneous melanoma. After the first month, he presented with grade 3 pyrexia (Common Terminology Criteria for Adverse Events [CTCAE] v.5.0.) and increased creatinine-kinase levels. A diagnosis of immune-mediated necrotizing myopathy, antisignal recognition particle (anit-SRP) positive, was made. At disease progression, dabrafenib/trametinib was restarted, triggering a new episode of grade 2 pyrexia and myositis. Treatment was changed to encorafenib/binimetinib without repeating pyrexia or limiting creatinine-kinase elevation, presenting even a loss of anti-SRP antibodies. Given the temporal relationship, the fact that re-exposition induced a new worsening of the myopathy and the loss of the anti-SRP antibodies after changing treatment, we infer that there possibly is a clear relationship between dabrafenib/trametinib treatment and the myopathy.

Encephalitis Associated With Immune Checkpoint Inhibitor Treatment in Patients With Melanoma.

Since the approval of immune checkpoint anti-programmed cell death protein 1 antibodies (pembrolizumab and nivolumab) and anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) in combination or monotherapy, significant advances have been made in the treatment of metastatic melanoma. The nonspecific immune stimulation resulting from these drugs can case a wide range of side effects in many organs including the nervous system, named immune-related adverse events. Few immune-related encephalitis associated with these antibodies have been described in the literature. It is a rare complication (<1% of the total of immune-related adverse events) but it can be fatal if not diagnosed and treated on time. We describe 3 cases of patients with melanoma, which were treated with a combination of ipilimumab-nivolumab (case 1), ipilimumab monotherapy (case 2), and nivolumab monotherapy (case 3), who developed an encephalitis which was related to immune checkpoint therapy.

Cognitive impairment following chemotherapy for breast cancer: The impact of practice effect on results.

Chemotherapy-Related Cognitive Impairment (CRCI) can be an adverse effect in women treated for breast cancer. Some longitudinal studies reported deficits in attention, memory, and executive function following treatment, but other studies did not find cognitive changes. It is known that practice effects (PE) on repeated assessments with cognitive tests contribute to the discrepancies in these results, but its influence on scores has not been systematically explored. The present study examines the impact of PE on retest scores in a group of women with breast cancer treated with chemotherapy and evaluated longitudinally. METHOD: 51 women with breast cancer treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide with or without taxanes were assessed after surgery but before chemotherapy (T1), post-chemotherapy (T2), and at one year after T2 (T3). Longitudinal changes on cognitive performance were analyzed twice: when retest scores were not corrected for PE and when correction for PE was applied to T2 and T3 scores. RESULTS: When PE was not corrected, progressive improvement over time in measures of memory and divided attention at T2 and T3 was observed. In contrast, when PE was corrected, worsening was found in measures of memory, fluency, executive function, and attention at T2 and in attention and executive function at T3. Results after correction for PE are in line with previous longitudinal studies that report cognitive impairment after treatment with chemotherapy for breast cancer. CONCLUSION: Accounting for PE is recommended to identify true change on cognition through treatment with chemotherapy for breast cancer.

Role of taxanes in chemotherapy-related cognitive impairment: A prospective longitudinal study.

PURPOSE: The aim of this study is to elucidate the role of taxanes on cognition when they are administered as a part of the treatment with a fluorouracil, epirubicin and cyclophosphamide (FEC) regimen for breast cancer (BC). METHODS: Two groups of women (n = 51) with a novel diagnostic of BC that were treated with a combination of FEC alone (6 cycles of FEC) or with taxanes (4 cycles of FEC plus 8 cycles of taxanes) were compared at three moments: before chemotherapy, after its completion (short-term evaluation) and at a mean of 74.5 weeks from baseline as a long-term evaluation. RESULTS: Both groups showed worsening in tests of attention and executive functions on the short-term assessment, with the group treated with taxanes showing more number of affected cognitive measures at this time point, including verbal learning and speed measures. At the long-term evaluation, cognitive dysfunction was still found in attention and executive functions in both groups. CONCLUSION: Our results suggest that chemotherapy for BC with a FEC regimen can have a negative effect on cognition. Acute deficits seem to be larger when taxanes are added, but treatment seems to affect cognition also at long term.

Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.

Incidence of chemotherapy-induced nausea and vomiting associated with docetaxel and cyclophosphamide in early breast cancer patients and aprepitant efficacy as salvage therapy. Results from the Spanish Breast Cancer Group/2009-02 study.

BACKGROUND: Docetaxel-cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients. PATIENTS AND METHODS: This prospective multicentre study enrolled 212 chemotherapy-naïve EBC patients receiving T-75 mg/m(2) and C-600 mg/m(2). Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT3) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2. RESULTS: Among the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2-91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8-72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8-38.1, p = 0.0124) and 2 (18.3-42.9, p = 0.0059). CONCLUSIONS: Guideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy.

Analysis of the pathologic response to primary chemotherapy in patients with locally advanced breast cancer grouped according to estrogen receptor, progesterone receptor, and HER2 status.

PURPOSE: In clinical practice, it is possible to classify breast tumors according to estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression: ER negative, PgR negative, and HER2 overexpressing; ER negative, PgR negative, and HER2 negative; ER positive, PgR positive, and HER2 negative; ER positive, PgR positive, and HER2 overexpressing; and the less frequent remaining 4 combinations. The aim of this study was to determine the percentage of pathologic complete response (pCR) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant or primary chemotherapy with anthracyclines and taxanes grouped according to ER, PgR, and HER2 status. PATIENTS AND METHODS: Patients with LABC treated with primary chemotherapy including anthracyclines and taxanes were grouped according to ER, PgR, and HER2 status; pCR rates were analyzed using the chi(2) test; and correlations with a P value of < or = 0.05 were considered statistically significant. RESULTS: A total of 103 patients were treated. Only 100 patients were included for the analysis of pCR. Eighteen patients exhibited pCR. The pCR rate for each subgroup was as follows: 39.1% (9 of 23) had ER-negative, PgR-negative, and HER2-negative disease (P < 0.01); 35.7% (5 of 14) had ER-negative, PgR-negative, and HER2-overexpressing disease; 33.3% (3 of 9) had ER-positive, PgR-positive, and HER2-overexpressing disease; and 2.8% (1 of 36) had ER-positive, PgR-positive, and HER2-negative disease (P < 0.01). CONCLUSION: In patients with LABC, grouping breast tumors according to ER, PgR, and HER2 status can help predict pCR to primary chemotherapy.