A phase II study of retifanlimab, a humanized anti-PD-1 monoclonal antibody, in patients with solid tumors (POD1UM-203).

BACKGROUND: POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy. PATIENTS AND METHODS: Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate. RESULTS: Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors. CONCLUSIONS: Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.

Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial.

BACKGROUND: The APPLE trial aimed to evaluate the feasibility of longitudinal plasma epidermal growth factor receptor (EGFR) T790M monitoring for the best sequencing strategy of gefitinib and osimertinib. METHODS: APPLE is a randomized, non-comparative, phase II study in patients with common EGFR-mutant, treatment-naive non-small-cell lung cancer including three arms: arm A (osimertinib upfront until RECIST progression, PD), arm B [gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation by cobas EGFR test v2 or RECIST PD], and arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms. The primary endpoint is the progression-free survival (PFS) rate 'on osimertinib' at 18 months (PFSR-OSI-18) after randomization in arm B (H0: PFSR-OSI-18 of ≤40%). Secondary endpoints include response rate, overall survival (OS), and brain PFS. We report the results of arms B and C. RESULTS: From November 2017 to February 2020, 52 and 51 patients were randomized into arms B and C, respectively. Most patients were females (70%) and had EGFR Del19 (65%); one-third had baseline brain metastases. In arm B, 17% of patients (8/47) switched to osimertinib based on the emergence of ctDNA T790M mutation before RECIST PD, with a median time to molecular PD of 266 days. The study met its primary endpoint of PFSR-OSI-18 of 67.2% (84% confidence interval 56.4% to 75.9%) in arm B versus 53.5% (84% confidence interval 42.3% to 63.5%) in arm C, with a median PFS of 22.0 months versus 20.2 months, respectively. The median OS was not reached in arm B versus 42.8 months in arm C. Median brain PFS in arms B and C was 24.4 and 21.4 months, respectively. CONCLUSIONS: The serial monitoring of ctDNA T790M status in advanced EGFR-mutant non-small-cell lung cancer during treatment with first-generation EGFR inhibitors was feasible, and a molecular progression before RECIST PD led to an earlier switch to osimertinib in 17% of patients with satisfactory PFS and OS outcomes.

Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy.

BACKGROUND: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown. PATIENTS AND METHODS: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions. RESULTS: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was ≥50% in 76 (25.2%), 1%-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pATB-exposed patients to have similar OS {hazard ratio (HR) = 1.42 [95% confidence interval (CI): 0.91-2.22]; P = 0.1207} and PFS [HR = 1.12 (95% CI: 0.76-1.63); P = 0.5552], compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% versus 57.4%, P = 0.1794). No differential effect was found depending on pATB exposure duration (≥7 versus <7 days) and route of administration (intravenous versus oral). Similarly, cATB was not associated with OS [HR = 1.29 (95% CI: 0.91-1.84); P = 0.149] and PFS [HR = 1.20 (95% CI: 0.89-1.63); P = 0.222] when evaluated as time-varying covariate in multivariable analysis. CONCLUSIONS: In contrast to what has been reported in patients receiving single-agent ICIs, pATB does not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinico-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus

Aim To stablish a consensus on the treatment strategy for advanced non–small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. Methods After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1–9 range scale (1–3 = disagree, 7–9 = agree). Consensus was reached if 2/3 of the participants are in the median range. Results In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. Conclusions A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations (AU)

SEOM clinical guideline for the management of cutaneous melanoma (2020)

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I–III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available (AU)

SEOM clinical guideline for the management of cutaneous melanoma (2020).

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.

Gender influence on work satisfaction and leadership for medical oncologists: a survey of the Spanish Society of Medical Oncology (SEOM).

BACKGROUND: Women represent an increasing proportion of the oncology workforce; however, globally this does not translate into leadership roles, reflecting disparities in career opportunities between men and women. The Spanish Society of Medical Oncology (SEOM) undertook a survey to investigate gender disparity in the Spanish oncology context. DESIGN: An online survey was made available to SEOM medical oncologists between February and May 2019. It included demographics, professional context and achievements, parenthood and family conciliation issues, workplace gender bias, and approaches to address disparities. RESULTS: Of the 316 eligible respondents, 71.5% were women, 59.5% were aged 45 or younger, and 66.1% had children. Among women, 12.4% were division or unit heads, compared with 45.5% of men, with most women (74.3%) being attending medical oncologists, compared with 45.5% of men. More males were professors (34.4% versus 14.2% of females), had a PhD (46.7% versus 28.8%), and/or had led clinical research groups (41.1% versus 9.7%). Spending time overseas after completing a residency was also more common for men than women (34.4% versus 20.4%). Professional satisfaction was similar between genders, driven primarily by patient care and intellectual stimulation. More women (40.7%) considered parenthood to have a strong negative impact on their career, compared with men (9.0%). Main perceived barriers to gender equality included a lack of work-life balance (72.6% women, 44.4% men), bias of peers and superiors (50.0% women, 18.9% men), and different career goals (41.2% women, 24.4% men). Preferred solutions included educational programs and scholarships (52.9%), communication and leadership training (35.8%), childcare at conferences (33.2%), and postmaternity return-to-work incentives (32.0%). CONCLUSION: There is a clear paucity of equal opportunities for female oncologists in Spain. This can be addressed by encouraging professional development and merit recognition particularly for younger female oncologists, and empowering women to be involved in management and leadership of institutions and professional societies.

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus.

AIM: To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. METHODS: After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree). Consensus was reached if 2/3 of the participants are in the median range. RESULTS: In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. CONCLUSIONS: A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations.

Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.

BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019).

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.

Multidisciplinary consensus statement on the clinical management of patients with stage III non-small cell lung cancer.

Stage III non-small cell lung cancer (NSCLC) is a very heterogeneous disease that encompasses patients with resected, potentially resectable and unresectable tumours. To improve the prognostic capacity of the TNM classification, it has been agreed to divide stage III into sub-stages IIIA, IIIB and IIIC that have very different 5-year survival rates (36, 26 and 13%, respectively). Currently, it is considered that both staging and optimal treatment of stage III NSCLC requires the joint work of a multidisciplinary team of expert physicians within the tumour committee. To improve the care of patients with stage III NSCLC, different scientific societies involved in the diagnosis and treatment of this disease have agreed to issue a series of recommendations that can contribute to homogenise the management of this disease, and ultimately to improve patient care.

Manejo clínico de los eventos adversos cutáneos en pacientes tratados con quimioterapia: consenso nacional de la Academia Española de Dermatología y Venereología y de la Sociedad Española de Oncología Médica / Clinical Management of Cutaneous Adverse Events in Patients on Chemotherapy: A National Consensus Statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology

A pesar del avance que ha supuesto en la supervivencia de los pacientes oncológicos, la aparición de nuevos agentes quimioterápicos y nuevas combinaciones, estos han traído consigo numerosos efectos adversos que pueden llegar a comprometer el tratamiento y, por consiguiente, el pronóstico de la enfermedad. Entre otros efectos secundarios los citostáticos pueden causar toxicidad dermatológica. El efecto adverso más conocido de la quimioterapia es la alopecia que, aunque no es grave, altera la apariencia externa de los pacientes con cáncer. Otros efectos adversos que pueden observarse son las reacciones de hipersensibilidad y fotosensibilidad, el síndrome mano-pie, la necrólisis epidérmica, las reacciones de reactivación, las reacciones esclerodermiformes, el fenómeno de Raynaud, la siringometaplasia escamosa ecrina, la hidradenitis neutrofílica ecrina, las alteraciones ungueales, las alteraciones en la pigmentación y las lesiones por extravasación. La aparición de estos efectos adversos produce en muchas ocasiones una reducción de dosis y/o retraso del tratamiento, lo que puede afectar a la supervivencia y a la calidad de vida del paciente. Por ello, es importante prevenir su aparición e instaurar un tratamiento temprano, para lo que se hace imprescindible la colaboración entre oncólogos médicos y dermatólogos. En este artículo se revisa la toxicidad dermatológica asociada con la quimioterapia, así como su diagnóstico y abordaje terapéutico

Although the arrival of new chemotherapy drugs and combinations has brought progress in terms of cancer patient survival, they entail many adverse effects that can compromise treatment, and hence prognosis, of the disease. Cytostatic agents can cause dermatological toxicity, among other side effects. The most familiar adverse effect of chemotherapy is alopecia. Although not serious, this changes the outward appearance of cancer patients. Other adverse effects include hypersensitivity and photosensitivity reactions, hand-foot syndrome, epidermal necrolysis, recall reactions, scleroderma-like reactions, Raynaud's phenomenon, eccrine squamous syringometaplasia, neutrophilic eccrine hidradenitis, nail abnormalities, pigmentation changes and extravasation injuries. Onset of these adverse effects often causes dose reduction and/or delayed treatment, which can affect patient survival and quality of life. It is therefore important to prevent their occurrence and treat them promptly, which requires cooperation between medical oncologists and dermatologists. This article reviews chemotherapy-associated dermatological toxicity, along with its diagnosis and therapeutic management

Clinical Management of Cutaneous Adverse Events in Patients on Chemotherapy: A National Consensus Statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology. / Manejo clínico de los eventos adversos cutáneos en pacientes tratados con quimioterapia: consenso nacional de la Academia Española de Dermatología y Venereología y de la Sociedad Española de Oncología Médica.

Although the arrival of new chemotherapy drugs and combinations has brought progress in terms of cancer patient survival, they entail many adverse effects that can compromise treatment, and hence prognosis, of the disease. Cytostatic agents can cause dermatological toxicity, among other side effects. The most familiar adverse effect of chemotherapy is alopecia. Although not serious, this changes the outward appearance of cancer patients. Other adverse effects include hypersensitivity and photosensitivity reactions, hand-foot syndrome, epidermal necrolysis, recall reactions, scleroderma-like reactions, Raynaud's phenomenon, eccrine squamous syringometaplasia, neutrophilic eccrine hidradenitis, nail abnormalities, pigmentation changes and extravasation injuries. Onset of these adverse effects often causes dose reduction and/or delayed treatment, which can affect patient survival and quality of life. It is therefore important to prevent their occurrence and treat them promptly, which requires cooperation between medical oncologists and dermatologists. This article reviews chemotherapy-associated dermatological toxicity, along with its diagnosis and therapeutic management.

Efficacy of nintedanib and docetaxel in patients with advanced lung adenocarcinoma treated with first-line chemotherapy and second-line immunotherapy in the nintedanib NPU program.

PURPOSE: Both nintedanib/docetaxel and anti-PD-1/PD-L1 immunotherapies have demonstrated efficacy as second-line treatment of patients with advanced lung adenocarcinoma. This is the first report on the efficacy of the nintedanib/docetaxel combination following first-line platinum-based chemotherapy and subsequent immunotherapy in a real-world setting. METHODS/PATIENTS: From May 2014 to December 2015, 390 patients in 108 Spanish centres enrolled in the nintedanib named patient use program. Inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. The objective was to evaluate the efficacy of the nintedanib/docetaxel combination in patients who also received immunotherapy. RESULTS: Eleven patients met the inclusion criteria; with a median age of 67 years. PD-L1 expression was positive in six patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (95% CI 1.9-4.6). Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) or nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (95% CI 0-6.1). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. Median PFS of nintedanib/docetaxel was 3.2 months (95% CI 1.9-4.5). Best response was partial response in four patients (36%), stable disease in five patients (46%), and progressive disease in two patients (18%), for an ORR of 36% and a DCR of 82%. CONCLUSION: Our experience suggests an encouraging efficacy of nintedanib/docetaxel in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy, reinforcing the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma.

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial.

BACKGROUND: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis. RESULTS: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01905657.

SEOM clinical guidelines on nutrition in cancer patients (2018).

Nutritional deficiency is a common medical problem that affects 15-40% of cancer patients. It negatively impacts their quality of life and can compromise treatment completion. Oncological therapies, such as surgery, radiation therapy, and drug therapies are improving survival rates. However, all these treatments can play a role in the development of malnutrition and/or metabolic alterations in cancer patients, induced by the tumor or by its treatment. Nutritional assessment of cancer patients is necessary at the time of diagnosis and throughout treatment, so as to detect nutritional deficiencies. The Patient-Generated Subjective Global Assessment method is the most widely used tool that also evaluates nutritional requirements. In this guideline, we will review the indications of nutritional interventions as well as artificial nutrition in general and according to the type of treatment (radiotherapy, surgery, or systemic therapy), or palliative care. Likewise, pharmacological agents and pharmaconutrients will be reviewed in addition to the role of regular physical activity.

SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018)

Non-small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. The last few years have seen the development of a new staging system, diagnostic procedures such as liquid biopsy, treatments like immunotherapy, as well as deeper molecular knowledge; so, more options can be offered to patients with driver mutations. Groups with specific treatments account for around 25% and demonstrate significant increases in overall survival, and in some subgroups, it is important to evaluate each treatment alternative in accordance with scientific evidence, and even more so with immunotherapy. New treatments similarly mean that we must reconsider what should be done in oligometastatic disease where local treatment attains greater value

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SEOM clinical guidelines on nutrition in cancer patients (2018)

Nutritional deficiency is a common medical problem that affects 15-40% of cancer patients. It negatively impacts their quality of life and can compromise treatment completion. Oncological therapies, such as surgery, radiation therapy, and drug therapies are improving survival rates. However, all these treatments can play a role in the development of malnutrition and/or metabolic alterations in cancer patients, induced by the tumor or by its treatment. Nutritional assessment of cancer patients is necessary at the time of diagnosis and throughout treatment, so as to detect nutritional deficiencies. The Patient-Generated Subjective Global Assessment method is the most widely used tool that also evaluates nutritional requirements. In this guideline, we will review the indications of nutritional interventions as well as artificial nutrition in general and according to the type of treatment (radiotherapy, surgery, or systemic therapy), or palliative care. Likewise, pharmacological agents and pharmaconutrients will be reviewed in addition to the role of regular physical activity

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