SEOM-GEM clinical guidelines for cutaneous melanoma (2023).

Cutaneous melanoma incidence is rising. Early diagnosis and treatment administration are key for increasing the chances of survival. For patients with locoregional advanced melanoma that can be treated with complete resection, adjuvant-and more recently neoadjuvant-with targeted therapy-BRAF and MEK inhibitors-and immunotherapy-anti-PD-1-based therapies-offer opportunities to reduce the risk of relapse and distant metastases. For patients with advanced disease not amenable to radical treatment, these treatments offer an unprecedented increase in overall survival. A group of medical oncologists from the Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines, based on a thorough review of the best evidence available. The following guidelines try to cover all the aspects from the diagnosis-clinical, pathological, and molecular-staging, risk stratification, adjuvant therapy, advanced disease therapy, and survivor follow-up, including special situations, such as brain metastases, refractory disease, and treatment sequencing. We aim help clinicians in the decision-making process.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

Follow-up of primary melanoma patients with high risk of recurrence: recommendations based on evidence and consensus.

In spite of the good prognosis of patients with early-stage melanoma, there is a substantial proportion of them that develop local or distant relapses. With the introduction of targeted and immune therapies for advanced melanoma, including at the adjuvant setting, early detection of recurrent melanoma and/or second primary lesions is crucial to improve clinical outcomes. However, there is a lack of universal guidelines regarding both frequency of surveillance visits and diagnostic imaging and/or laboratory evaluations. In this article, a multidisciplinary expert panel recommends, after careful review of relevant data in the field, a consensus- and experience-based follow-up strategy for melanoma patients, taking into account prognostic factors and biomarkers and the high-risk periods and patterns of recurrence in each (sub) stage of the disease. Apart from the surveillance intensity, healthcare professionals should focus on patients' education to perform regular self-examinations of the skin and palpation of lymph nodes.

Molecular basis of hypertension side effects induced by sunitinib.

Over the past decade a number of vascular complications have emerged, such as newly developed or worsened hypertension, in patients who were administered with new cancer treatments for several types of cancer that were untreatable earlier. Hypertension is emerging as one of the most common adverse effects of therapy with angiogenesis inhibitors. Small-molecule inhibitors of vascular endothelial growth factor signalling are associated with a high proportion of patients with hypertension. The mechanisms underlying the development of hypertension are not well known, although there seem to be several mechanisms. Physiopathology of hypertension implicates abnormalities in endothelial function and angiogenesis. Several features of hypertensive patients are reduced number of arterioles and capillaries, alterations of the microvascular network, decrease in vascular wall compliance and flexibility, reduced nitric oxide bioactivity and increases in plasma vascular endothelial growth factor. Treatment with tyrosine kinase inhibitors (TKIs) is associated with a significant and sustained increase in blood pressure. We suspect that TKIs exert their hypertensive effects directly at the level of the microvascular network through processes such as vascular rarefaction, endothelial dysfunction and/or altered nitric oxide metabolism. This study shows the vascular complications of treatment with a TKI, sunitinib (SU11248), with special emphasis on hypertension.

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis.

This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667-0.783, p = 0.002), and grade 3-5 AEs (RR = 0.406 95% CI: 0.340-0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29-0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs.

Durable Response to Vemurafenib and Cobimetinib for the Treatment of BRAF-Mutated Metastatic Melanoma in Routine Clinical Practice.

BACKGROUND: The combination of BRAF and MEK inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a BRAF inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings. PATIENTS AND METHODS: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAF V600 mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019. Participants were differentiated regarding the durability of the response: durable (complete response, CR, or a partial response, PR, for at least 12 months) and non-durable (stable disease, SD, progressive disease, PD, or CR/PR <12 months). Secondary endpoints included treatment adherence, labor productivity, anxiety/depression, and safety profile. RESULTS: During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD. A total of 12 patients (29.3%) were considered as achieving a durable response and 29 (70.7%) as a non-durable one. Practically all sociodemographic and clinical characteristics were similar between patients. Body mass index was the only differential factor (with higher body mass index achieving a non-durable response). The treatment adherence was 100% in patients with durable response and 66.7% in those with non-durable. CONCLUSION: The combination treatment with vemurafenib/cobimetinib results in an important impact on long-term survival, leading to a steady CR in one-third of the patients.

Efficacy and safety of Nivolumab in older patients with pretreated lung cancer: A subgroup analysis of the Galician lung cancer group.

BACKGROUND: Nivolumab is an anti PD1 immunotherapy drug approved for advanced Non-Small Cell Lung Cancer (NSCLC) patients who previously received at least one prior line of treatment. Older patients are often not represented in clinical trials and drugs with acceptable safety profiles are necessary. We aim to report the efficacy and safety profile of Nivolumab in the real-world older subgroup of the Galician lung cancer group study. PATIENTS AND METHODS: We retrospectively reviewed 188 advanced NSCLC patients treated with at least one prior therapy. We collected data from patients who were ≥70 years old treated with Nivolumab in second or subsequent lines. Patient characteristics, treatment efficacy (overall survival, progression-free survival, and response rate), and safety profile were reported. RESULTS: Thirty-eight patients aged ≥70 years were included in the subgroup analysis. The median age was 74.5 years, a high percentage of patients were males (95%), most had a Performance Status of 1 (79%) and only 13% were non-smokers. The predominant histology was adenocarcinoma (53%), and 18% of patients received 2 or more lines. The median Progression-Free Survival was 7.53 months (CI 4.3-17.3, p = 0.15) and the median Overall Survival was 14.85 months (CI 10.5-20.7, p = 0.44). The objective response rate was 42%. No new adverse events were reported in comparison to a global population. CONCLUSIONS: The efficacy and safety profile of Nivolumab in advanced NSCLC patients treated with at least one prior therapy and age ≥70 years old can be overlapped to a global population. Further prospective trials are needed to define and confirm these results.

Prognostic factors for survival in patients with metastatic lung adenocarcinoma: An analysis of the SEER database.

BACKGROUND: Lung adenocarcinoma (ADC) is the main cause of death related to lung cancer. The aim of this study was to identify poor prognostic factors for overall survival (OS) in patients with stage IV lung ADC in real-world clinical practice. METHODS: Patients were selected from the Surveillance Epidemiology and End Results (SEER) database. Chi-square bivariate analysis was used for the association of binary qualitative variables. A multivariate Cox regression analysis was performed to determine the impact of these prognostic factors on OS. RESULTS: A total of 46 030 patients were included (51.3% men, mean age 67.03 ± 11.6), of whom 41.3% presented with metastases in bone, 28.9% in brain, 17.1% in liver and 31.8% in lung. Patients with liver metastases presented with two or more metastatic sites more frequently than patients without liver metastases (P < 0.001). Male sex (HR 0.78, 95% CI: 0.76-0.80), age ≥ 65 years (HR 1.37, 95% CI: 1.33-1.40), lack of family support (HR 0.80, 95% CI: 0.78-0.81) and presence of liver (HR 1.45, 95% CI: 1.40-1.50), bone (HR 1.21, 95% CI: 1.18-1.24) or brain metastases (HR 1.18, 95% CI: 1.15-1.21) were identified as poor prognostic factors for OS. Patients with liver metastasis showed the highest hazard ratio value (P < 0.001). CONCLUSIONS: The presence of liver metastases was the worst prognostic factor for patients with metastatic lung ADC. This factor should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Regression analysis identified poor prognostic factors for overall survival. Factors were male sex, age ≥ 65 years, lack of family support and presence of liver, bone and brain metastases. Patients with liver metastasis showed the highest HR (HR = 1.45 95% CI: 1.40-1.50). This study included the highest number of adenocarcinoma patients analyzed so far (N = 46 030). What this study adds The presence of liver metastases should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy.

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis.

The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group

Purpose Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. Methods/patients Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. Results 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01–34.2 vs. 27 months, 95% CI 22.6–31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4–37.6 vs 25 months, 95% CI 20.7–29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). Conclusions There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer (AU)

Real world data of nivolumab for previously treated non-small cell lung cancer patients: a Galician lung cancer group clinical experience.

BACKGROUND: Recently, immunotherapy has changed the standard of treatment in non-small cell lung cancer (NSCLC). Outside clinical trials, data of real life is lacking. This is an observational study that represents the real world experience with nivolumab in pretreated NSCLC. METHODS: Eligibility criteria included, histologically confirmed NSCLC, stage IIIB and IV, evaluable disease and at least one prior therapy. Patients received nivolumab until progressive disease (PD) or unacceptable toxicity. The main aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The secondary aim was to perform subgroup analysis by clinical features. RESULTS: From August of 2015 to January of 2017, 188 patients were enrolled. The patients demographics were: median age 58 years, 144 male; 17 never smoker and 171 former/current smoker; 112 adenocarcinoma, 66 squamous-cell carcinoma and 10 not otherwise specified (NOS); 61 stage IIIB and 127 stage IV; 15 performance status (PS) 0, 154 PS 1 and 19 PS 2; 5 epidermal growth factor receptor (EGFR) and 1 anaplastic lymphoma kinase (ALK); 42 with central nervous system (CNS) metastases; and 71 received 2 or more prior therapy lines. Of the 188 patients enrolled, 25 (13.3%) were not evaluated, 3 (1.6%) had complete response (CR), 45 (23.9%) partial response (PR), 48 (25.5%) disease stabilization (DS) and 67 (35.6%) PD. The median of progression-free survival (PFS) was 4.83 months (95% CI, 3.6-5.9) and overall survival (OS) was 12.85 months (95% CI, 9.07-16.62). The subgroup analysis revealed statistical significance in OS for patients with CNS metastases 14.8 months (95% CI, 11.5-17.3) vs. 5.09 months (95% CI, 0.3-9.8) and also PS 0 [not reached (NR)] vs. PS 1 11.7 months vs. PS 2 3.4 months (95% CI, 2.3-4.4). The safety profile was in accordance with the literature data. CONCLUSIONS: This study represents the real word experience with nivolumab and the results are consistent with previously reported in clinical trials. PS 2 and the presence of CNS metastases are associated with poor prognosis.

Follow-up of primary melanoma patients with high risk of recurrence: recommendations based on evidence and consensus

In spite of the good prognosis of patients with early-stage melanoma, there is a substantial proportion of them that develop local or distant relapses. With the introduction of targeted and immune therapies for advanced melanoma, including at the adjuvant setting, early detection of recurrent melanoma and/or second primary lesions is crucial to improve clinical outcomes. However, there is a lack of universal guidelines regarding both frequency of surveillance visits and diagnostic imaging and/or laboratory evaluations. In this article, a multidisciplinary expert panel recommends, after careful review of relevant data in the field, a consensus- and experience-based follow-up strategy for melanoma patients, taking into account prognostic factors and biomarkers and the high-risk periods and patterns of recurrence in each (sub) stage of the disease. Apart from the surveillance intensity, healthcare professionals should focus on patients’ education to perform regular self-examinations of the skin and palpation of lymph nodes. (AU)

[Venous thrombosis of atypical location in patients with cancer]. / Trombosis venosa de localización atípica en pacientes con cáncer.

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary).

Trombosis venosa de localización atípica en pacientes con cáncer / Venous thrombosis of atypical location in patients with cancer

La enfermedad tromboembólica venosa (ETEV) es una complicación que se presenta con frecuencia en los pacientes con enfermedades neoplásicas; por ello se han desarrollado varios modelos para identificar subgrupos de pacientes diagnosticados de cáncer con riesgo aumentado de desarrollar ETEV. Las localizaciones más frecuentes de los episodios tromboembólicos son la trombosis venosa profunda en miembros inferiores y la tromboembolia pulmonar, sin olvidar que se diagnostican trombosis venosas en localizaciones atípicas. Apenas hay revisiones sobre trombosis venosas inusuales; en la mayoría de los casos, la localización más frecuente es en miembros superiores y en relación con la presencia de catéteres venosos centrales, marcapasos y desfibriladores. Presentamos el caso de una paciente diagnosticada de cáncer de mama y tratada con cirugía, quimioterapia y radioterapia que presentó una trombosis en miembros superiores (humeral y axilar) (AU)

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary) (AU)