BackgroundTargeted therapies and immunotherapy are currently considered the mainstay first-line treatment for advanced BRAF-mutated melanoma. However, the impact of treatment (targeted therapy and immunotherapy) and the prognostic factors are still not clear.Material and methodsMedical records of 140 patients diagnosed with advanced melanoma between 2011 and 2021 were retrospectively reviewed to extract demographic, BRAF status, treatment, performance status, and survival data. ORR, PFS, and OS were compared between patients diagnosed with advanced melanoma and treated with first-line IT or BRAF/MEKi. The prognostic factors were assessed using Cox regression models.ResultsIn all patients and those treated with immunotherapy, we did not find any effect of BRAF status on ORR, PFS, or OS. In patients with BRAF-mutated melanoma, ORR was 43.8% vs. 70% (P=0.04), PFS was 19.2 vs. 11.5 months (p=0.22), and OS was 33.4 vs. 16.4 months for the immunotherapy and targeted therapy groups, respectively (P=0.04). ECOG, presence of brain metastases, and high LDH level from initiation of first-line treatment were all associated with differences in PFS and OS.ConclusionPatients with advanced BRAF-mutated melanoma treated with first-line immunotherapy had a significantly longer PFS and OS than those treated with first-line BRAF/MEKi; however, first-line BRAF/MEKi treatment had a significantly higher ORR than first-line immunotherapy.

Introduction: Immune checkpoint inhibitors (ICIs) have radically changed the prognosis of several neoplasias, among them metastatic melanoma. In the past decade, some of these new drugs have appeared together with a new toxicity spectrum previously unknown to clinicians, until now. A common situation in daily practice is that a patient experiences toxicity due to this type of drug and we need to resume or rechallenge treatment after resolving the adverse event. Methods: A PubMed literature review was carried out. Results: The published data regarding the resumption or rechallenge of ICI treatment in melanoma patients is scarce and heterogeneous. Depending on the study reviewed, the recurrence incidence of grade 3–4 immune-related adverse events (irAEs) ranged from 18% to 82%. Conclusion: It is possible to resume or rechallenge, but each patient should be evaluated by a multidisciplinary team for close monitoring and assessment of the risk/benefit ratio before initiating treatment.

Citation: Verdaguer Faja J, Manzano JL, España S, Notta PC, Rodriguez Iniesta RV, Boada A. Lymphadenopathy After COVID-19 Vaccine Mimicking Lymph Node Progression in a Patient With Metastatic Melanoma. Dermatol Pract Concept. 2022;12(4):e2022171. DOI: https://doi.org/10.5826/dpc.1204a171

Efficacy and safety of dabrafenib and trametinib in metastatic melanoma have been demonstrated in two-phase III and one-phase I/II clinical trials. However, patients at least 75 years old (y.o.) were largely underrepresented. Additionally, the safety profile of dabrafenib and trametinib based on age is unknown. ELDERLYMEL is a retrospective noninterventional multicenter study, describing the effectiveness and safety of at least 75 y.o. patients compared with less than 75 y.o. patients with advanced BRAF V600-mutated melanoma treated with dabrafenib plus trametinib or dabrafenib monotherapy. A total of 159 patients were included, 130 less than 75 y.o. and 29 at least 75 y.o. Clinical features were similar between the groups, except in the number of comorbidities, number of metastatic sites, Eastern Cooperative Oncology Group (ECOG) performance status, and BRAF V600-mutation type. Five patients per group received dabrafenib monotherapy. There were no differences in adverse events (AEs) rate or grade between the groups. However, AE profiles were different between the groups, being pyrexia infrequent in patients at least 75 y.o. (13.8% vs. 42.3%; P = 0.005). Dabrafenib and trametinib dose intensities were lower in at least 75 y.o. patients (P = 0.018 and P = 0.020), but there were no differences in effectiveness between the groups. Finally, in a multivariate analysis, sex (female) was the only variable independently associated with an increased risk of AE grade ≥3. Data from the ELDERLYMEL study demonstrate that dabrafenib plus trametinib is safe and effective in at least 75 y.o. patients with advanced BRAF V600-mutated melanoma without increasing toxicity. Additionally, we describe a different safety profile depending on age and sex.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. Moreover, it is associated with a higher cardio-metabolic risk than the observed in patients with essential hypertension (EHT). Therefore, a high index of clinical suspicion for PA is mandatory. If an elevated aldosterone/renin ratio is confirmed, confirmatory tests should be performed, with the exception in those patients with florid PA, with, with spontaneous hypokalaemia, plasma aldosterone> 20 ng/dl and suppressed renin, in whom this step would not be strictly necessary. Saline infusion test or captopril test are de commonly used confirmatory tests. The last step in the diagnosis of PA is the localization study, being the computerized axial tomography (CT) of the adrenal glands the initial test of choice, and adrenal venous sampling (AVS), the definitive localization test in most cases. This review summarizes the available data about the diagnosis of PA, from screening to confirmatory study and localization.El hiperaldosteronismo primario (HAP) es la forma más frecuente de hipertensión secundaria, y se asocia a un mayor riesgo cardio-metabólico que el observado en pacientes con HTA esencial. Por tanto, es preceptivo mantener un alto índice de sospecha clínica. Si se confirma un cociente aldosterona/renina elevado se deben realizar pruebas de confirmación, habitualmente una prueba de sobrecarga salina o de captopril, salvo en pacientes con HAP franco, con hipopotasemia espontánea, aldosterona plasmática >20 ng/dl y renina suprimida, en los que no sería estrictamente necesario este paso. El último paso en el diagnóstico es el estudio de localización, siendo la tomografía axial computarizada (TC) de suprarrenales la prueba inicial de elección, y el cateterismo de venas adrenales (CVA), la prueba definitiva de localización en la mayor parte de los casos. En esta revisión se resumen los datos sobre el diagnóstico del HAP, desde el cribado al estudio de confirmación y de localización.

In recent years, studies on the molecular typing of colorectal cancer have matured, and the V-raf murine sarcoma viral oncogene homolog B (BRAF) of the mitogen-activated protein kinase pathway has been shown to be an important effector molecule of this pathway and regulates the occurrence and development of colorectal cancer. Clinical observations indicate that colorectal cancer patients harboring the BRAF V600E mutation have a worse prognosis than BRAF wild type patients. Several resistance mechanisms have been identified that have led to the development of different treatment strategies, which have shown encouraging activity in early clinical trials. Therefore, a reasonable combination of targeted therapies is expected to further enhance the efficacy of selective BRAF inhibitors. Moreover, some CRC patients with high microsatellite instability or a mismatch repair deficiency seem to be susceptible to checkpoint inhibitors with objective and sustained clinical responses, providing new opportunities for patients with advanced disease. This article primarily explores 3 aspects of the treatment strategies for advanced BRAF-mutated colorectal cancer; chemotherapy, targeted therapy, and immunotherapy.

The Naloxegol Cancer Study (NACASY) was a multinational European study aimed to evaluate the 4-week safety and efficacy of naloxegol in a real-world setting in patients with cancer pain diagnosed with opioid-induced constipation. The primary safety endpoint was the incidence of adverse events leading to study discontinuation. We recruited 170 patients who received at least one dose of naloxegol (i.e., safety population). Out of 170 patients, 20 (11.8%, 95%CI 6.9–16.6) discontinued the study due to adverse events, and, of them, 12 (7.1%, 95%CI 3.2–10.9%) were study discontinuations due to naloxegol-related adverse events. From 76 patients subjects who had completed both 4 weeks of treatment and 28 days of the diary, 55 patients (72.4%, 95% CI 62.3–82.4%) were regarded as responders (i.e., showed ≥3 bowel-movements per week and an increase of ≥1 bowel-movement over baseline) to naloxegol treatment. The Patient Assessment of Constipation—Quality of Life Questionnaire total score and all its subscales improved from baseline to 4 weeks of follow up. Our findings support and provide new evidence about the beneficial effect of naloxegol in terms of improvement of constipation and quality-of-life in patients with cancer-related pain and opioid-induced constipation and show a safety profile consistent with previous pivotal and real-world studies.

2544 Background: Cancer patients (pts) represent a high-risk population for severe COVID-19. Cancer-associated immunosuppression may hinder in the development of anti-SARS-CoV-2 antibodies. Methods: Data regarding baseline characteristics, COVID-19 and anti-SARS-Cov2 IgG were collected from cancer pts (solid tumors) who tested positive for COVID-19 (PCR+) between March and April 2020 at Catalan Institute of Oncology. We prospectively assessed anti-SARS-Cov2 IgG seroprevalence at 3 and 9 months post infection and explored clinico-pathologic factors associated with IgG positivity. We explored the impact of potential factors influencing antibody production at >9 months. Results: Of 49 pts registered between 10 th March-26 th April 2020, 21 died <3 months after the infection and 5 pts refused to participate, leaving 23 eligible pts for IgG testing. With respect to those not tested, IgG tested cohort was younger (median age: 64.0 vs 72.9 years, p = 0.001) and presented oncologic remission in 68.2% of cases (vs 34.6%, p = 0.043) at COVID-19 diagnosis. Median time from PCR+ to first and second IgG determination was 3.2 months (Interquartile range [IQR]: 2.9-4.1) and 9.5 months (IQR: 8.8-9.8), respectively. Out of 23 pts, 15 had both determinations and 8 had only one (3 in the first time point, 5 in the second one). We identified 16/18 pts IgG+ (88.9%) at 3 months and 17/20 pts IgG+ (85%) at 9 months. One IgG+ pt became IgG- at the second determination, one was IgG- at both timepoints, and one had an inconclusive result at the first but negative at the second timepoint. Key characteristics of patients by IgG result 9 months after COVID-19 diagnosis are shown in the table. Conclusions: We describe a high seroprevalence of anti-SARS-CoV-2 IgG at 3 and 9 months after COVID-19 diagnosis in solid tumour patients, irrespective of anti-cancer therapy exposure. Pts who were IgG+ at 9 months were older, and more likely to have required oxygen during prior COVID-19 in comparison to IgG- pts suggesting that infection severity may promote durable immunity. Frequency of early stage cancers was higher among IgG+ pts, suggesting less cancer-related immunosupression. Older (>70 years) and advanced cancer pts were under-represented in this series, warranting confirmation of these preliminary results in a larger cohort.[Table: see text]

Background: Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially associated with overall survival (OS) in patients treated with AA. Methods: Between 2011 and 2014, 104 patients with mCRPC treated with AA after progression to docetaxel at centers of the Catalan Institute of Oncology were included in this retrospective study. Patients were assessed monthly. Baseline characteristics and variables related to PSA kinetics were included in univariate and multivariate analyses of OS. Results: Median OS was 16.4 months (range 12.4-20.6) for all patients. The univariate analysis identified the following baseline characteristics as significantly associated with OS: ECOG PS, location of metastases, time between starting androgen deprivation therapy and starting AA, time between stopping docetaxel treatment and starting AA, neutrophillymphocyte ratio (NLR), alkaline phosphatase levels, and PSA levels. Factors related to PSA kinetics associated with longer OS were PSA response >50%, early PSA response (>30% decline at four weeks), PSA decline >50% at week 12, PSA nadir <2.4ng/mL, time to PSA nadir >140 days, the combination of PSA nadir and time to PSA nadir, and low end-of-treatment PSA levels. The multivariate analysis identified ECOG PS (HR 37.46; p<0.001), NLR (HR 3.7; p<0.001), early PSA response (HR 1.22; p=0.002), and time to PSA nadir (HR 0.39; p=0.002) as independent prognostic markers. Conclusion: Our results indicate an association between PSA kinetics, especially early PSA response, and outcome to AA after progression to docetaxel. Taken together with other factors, lack of an early PSA response could identify patients who are unlikely to benefit from AA and who could be closely monitored with a view to offering alternative therapies.

BACKGROUND:Immune-oncology agents (IOA) represent a turning point in the treatment of several solid tumors (ST). Although their toxicity compares favorably with other treatments, IOA associate immune-related adverse events (IR-AE), among which endocrine-related AE stand out. We retrospectively evaluated the occurrence of endocrine (E) IR-AE in a cohort of patients with several ST treated with IOA. In addition, we assessed the correlation between likelihood of survival and the occurrence of IR-AE.METHODS:We collected data on clinical and molecular characteristics, efficacy and AE of 260 patients with ST treated with IOA from 2013 to 2017. We excluded patients with prior conditions or treatments potentially affecting thyroid test results.RESULTS:Lung cancer was the most prevalent diagnosis (70.2%). EIR-AE appeared in 18.1% of patients (total of 38 EIR-AE) and consisted of hypothyroidism, hyperthyroidism, pituitary disorders and type 1 diabetes mellitus in 60.5%, 21.1%, 15.8% and 2.6% of patients, respectively. EIR-AE were associated mainly to nivolumab, nivolumab plus ipilimumab (41.2% and 26.5%) and appeared after a median of 4.2 cycles of treatment. Specific therapy was required in 65.8% patients. There were significant differences in both progression-free survival (PFS) and overall survival (OS) for patients who experienced EIR-AE compared to those who did not [PFS: 56.7 (NC-NC) vs. 27.7 (14.3-41.3) months, P=0.008; OS: NC (NC-NC) vs. 31.4 (20.7-42.1) months, P=0.001].CONCLUSIONS:The incidence of EIR-AE in our study is similar to other series. Patients who develop EIR-AE might have a better prognosis compared to those who do not experience them.

e17066 Background: Identifying high-risk early-stage EOC patients (p) is a major issue. Also, controversy about the role of neoadjuvant chemotherapy prior to surgery in advanced EOC is still ongoing. A high MLR is related to poorer outcomes in several cancers, and also in ovarian cancer according to limited retrospective series. We explored the clinical value of MLR in a cohort of EOC p. Methods: We included all EOC p diagnosed in our center, from January 2008 to April 2017, who had undergone radical treatment. Overall survival (OS) was assessed by Kaplan Meyer. Maximally selected rank statistics was used to determine the MLR cut-off value for the greatest OS discrimination. The hazard ratio (HR) of death of MLR was explored by multivariate Cox regression models, adjusted by age at diagnosis, stage I/II versus (vs) III/IV, high grade serous carcinomas (HGSC) vs other, primary surgery vs interval surgery after neoadjuvant chemotherapy (PS, IS), residual disease < 1 vs > 1cm, year of diagnosis, and hemoglobin, neutrophils, platelets and MLR at diagnosis. Results: 124 p were included. Median age at diagnosis was 58.7 years; 55.6% were HGSC;67.7% stage III/IV; 69.3% received PS; 14.3% had residual disease > 1cm. Median OS was 75 months. MLR was the laboratory parameter that more significantly impacted on OS in our model (p = 0.02). Optimal MLR cut-off was 0.38. The MLR > 0.38 group (MLR-hi) had a higher-risk of death (HR = 2.9; 95% IC: 1.3–6.5) with respect to those with MLR < = 0.38 (MLR-lo). Median OS were 100 and 35 months, respectively. In the MLR-lo group, median age at diagnosis was 56.9 years (vs 61.9 in the MLR-hi, p 0.047), 44.8% were HGSC (vs 61.2%, p 0.134), and 49.97% were stages I/II (vs 14.2%, p 0.001). MLR-hi p who had undergone PS or IS had similar OS (p = 0.63). In contrast, among MLR-lo p, PS showed significantly higher OS than IS (p < 0.0001). Conclusions: In our cohort, MLR was an independent prognostic factor in EOC. Its potential role to identify high-risk early-stage p and to predict worse outcomes after PS among advanced-stage p need to be explored in larger cohorts.

T-DM1 is an antibody drug conjugate that combines trastuzumab with emtansine via a stable thioether linker. In two phase III clinical trials, EMILIA and TH3RESA, T-DM1 was shown to be effective in HER2-positive metastatic breast cancer patients who had progressed to taxanes and trastuzumab. We have performed a real-world study to complement the findings of the clinical trials. From 2012 to 2016, 15 patients with HER2-positive breast cancer who had progressed to prior treatment received T-DM1 at our center. We have retrospectively analyzed outcomes in these patients and compared our findings with those of the two clinical trials. Progression-free survival (PFS) was 10 months compared with the 9.6 months of the EMILIA trial and the 6.2 months of the TH3RESA trial, overall survival was 34 months compared with the 29.9 months of the EMILIA trial and the 22.7 months of the TH3RESA trial. PFS was ≥12 months in five patients, three of whom attained a PFS of ≥23 months. Among five patients with metastases of the central nervous system, PFS was six months, OS was not reached, and the objective response rate was 80%. Our findings are in line with those of the EMILIA study and slightly superior to those of the TH3RESA study. In our series of patients, T-DM1 has demonstrated efficacy in the treatment of HER2-positive metastatic breast cancer. Our real-world data thus confirm and support the findings of the two major phase III trials and indicate the usefulness of T-DM1 in routine clinical practice.

e13060 Background: Sequential endocrine therapy is the usual practice strategy for p with ER+/Her2- MBC. Last years, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors may change the gold standard of treatment in first line. The increase of cost to treat all the p with CDK4/6 inhibitors could be an important effort for public institutions. Furthermore, any clinical trial has showed evidence of overall survival (OS) benefit in front of endocrine therapy. We hypothesize which p may have good response to the sequential endocrine therapy. Methods: We perform a retrospective analysis of 179 p with ER+/HER2- MBC visited in medical oncology service in our centre (ICO-Badalona) from 2004 to 2014, treated with hormonal therapy. Males were excluded. We categorized different group p, such as age at diagnosis (per decades), metastatic side affected at metastatic diagnosis (3 groups: only bone, bone plus other and visceral) and time to relieve (4 groups: de novo, less than 2 years with hormonal adjuvant treatment, from 2 years to 6 years, and more than 6 years after radical treatment). Results: Describing all p, median age at MBC diagnosis was 56 y, and OS was 44,4 m (IQ 95%: 36,5-52,3). Most of the p (68,8%) received more than 2 lines of treatment. Analysing all p characteristics and different groups of patients, we found two main influence landscapes in OS: First of all, organ involvement; where visceral disease at metastatic situation had worst prognosis (median OS: 36,5 m) and inversely, but also significative, those with only bone involvement has better prognosis (median OS 101,5 m); second, those p with a late recurrence after a radical treatment has a better prognosis (median OS: 103,5). Conclusions: A clinical algorithm could help to choose which p may benefit from endocrine sequence therapy. Those p with bone only and those p with late recurrence without visceral affection could benefit from an endocrine therapy alone because of the better prognosis that presented, awaiting survival results of CDK 4/6 inhibitors. CDK4/6 inhibitors could be indicated in first line in the rest of p and added in second line in this subset of good prognostic patients.