Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic NSCLC.

INTRODUCTION: Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed. PATIENTS AND METHODS: The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis. RESULTS: The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient's sera inhibited the EGFR pathway in tumor cells growing in vitro. CONCLUSIONS: Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

Expression-based, consistent biomarkers for prognosis and diagnosis in lung cancer.

OVERVIEW: Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. MATERIAL AND METHODS: High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). RESULTS: A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. CONCLUSIONS: This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019).

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study.

BACKGROUND: Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). METHODS: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported. RESULTS: Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated. CONCLUSIONS: After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1-negative patients. Long-term survival was not limited to responders.

Factores asociados al ataque cerebrovascular isquémico entre los años 2013 a 2016, un estudio de casos y controles / Factors associated with ischaemic cerebrovascular accidents between the years 2013 and 2016: A case-control study

Resumen Objetivo: Determinar los factores asociados al ataque cerebrovascular isquémico en el servicio de urgencias de la Clínica Especializada Los Andes, de la ciudad de Tunja, entre los años 2013 a 2016. Pacientes y métodos: Estudio de casos y controles; los casos correspondieron a 97 pacientes con ataque cerebrovascular isquémico (infarto cerebral isquémico y accidente isquémico transitorio) y los controles a 291 pacientes sin ataque cerebrovascular isquémico que ingresaron a urgencias entre los años 2013 a 2016. Resultados: El sexo femenino correspondió al 56,7% (55) de los casos y al 54,6% de los controles (154) (p = 0,069). La media de edad en el grupo caso fue de 73,7 años ENT#091;DE: 10,5 añosENT#093; y en los controles de 64,5 años ENT#091;DE: 11,3 añosENT#093;. Los factores asociados al ataque cerebrovascular isquémico fueron: antecedente de ataque cerebrovascular isquémico ENT#091;OR 7,7 IC 95% 3,2; 18 p= 0,000ENT#093;, tabaquismo ENT#091;OR 4,4 IC 95% 1,1; 18 p= 0,022ENT#093;, dislipidemia ENT#091;OR 3 IC 95% 1,2; 7,5 p= 0,017ENT#093;, edad igual o mayor a 70 años ENT#091;OR 2,3 IC 95% 1,3; 4,1 p= 0,002ENT#093; e hipertensión arterial ENT#091;OR 1,8 IC 95% 1,06; 3,3 p= 0,029ENT#093;. Conclusiones: Los factores asociados al ataque cerebrovascular isquémico fueron, en orden de importancia, antecedente de ataque cerebrovascular isquémico, tabaquismo, dislipidemia, edad igual o mayor a 70 años E hipertensión arterial.

Abstract Objective: To determine the factors associated with ischaemic cerebrovascular accidents (ICVA) in the Emergency Department of the Andes Specialist Clinic of the city of Tunja, between the years 2013 and 2016. Patients and methods: A case-control study was conducted in which the cases consisted of 97 patients with ICVA (ischaemic cerebral infarction and transient ischaemic accident), and the controls were 291 patients with no ICVA, who were admitted to the Emergency Department between the years 2013 and 2016. Results: There were 56.7% (55) females in the cases, and 54.6% (154) in the controls (P=.069). The mean age of the cases was 73.7 years ENT#091;SD: 10.5 yearsENT#093;, and 64.5 years ENT#091;SD: 11.3 yearsENT#093; in the controls. The factors associated with ICVA were: a history of ICVA ENT#091;OR; 7.7, 95% CI; 3.2-18, P=.000ENT#093;, smoking ENT#091;OR; 4.4, 95% CI; 1.1-18, P=.022ENT#093;, dyslipidaemia ENT#091;OR; 3, 95% CI; 1.2-7.5, P=.017ENT#093;, age equal to or greater than 70 years ENT#091;OR; 2.3, 95% CI; 1.3-4.1, P=.002ENT#093;, and arterial hypertension ENT#091;OR; 1.8, 95% CI; 1.06-3.3, P=.029ENT#093;. Conclusions: The factors associated with ischaemic cerebrovascular accident were, in order of importance, a history of ischaemic cerebrovascular accident, smoking, dyslipidaemia, age equal to or greater than 70 years, and arterial hypertension.

Evaluation of scientific output in Dentistry in Spanish Universities.

BACKGROUND: The aim of this study was to assess the scientific output of Spanish universities that offer a bachelor's degree in dentistry through the use of various bibliometric indicators. MATERIAL AND METHODS: A total of 21 universities offered a bachelor's degree in dentistry in academic year 2016-2017. The search for papers published by authors associated with these institutions was carried out using the selection of journals listed in the Journal Citation Reports (JCR) and the Web of Knowledge database for the period 1986-2017. On the basis of these data, we determined the output, the h-, g- and hg-indexes, the most productive authors, international collaborations, and the most relevant journals. RESULTS: Public universities obtained better results than private universities. The University of Valencia was ranked first, followed by the Complutense University of Madrid and the University of Granada. The most productive author was José Vicente Bagán, but the author with the highest h-index was Mariano Sanz and Manuel Toledado. The universities with the greatest output and highest citation rates had more international collaborations. The most developed fields in Spanish universities were Oral surgery, Oral medicine and Dental materials. The universities had different models of production. At universities such as Barcelona or Valencia, the production was focused on very few departments and authors. At the other extreme, the University of Granada had various sources of research and authors, which meant that its output and citation rate could increase more. CONCLUSIONS: University faculties must provide suitable academic and research training, and therefore must be assessed using objective criteria and bibliometric tools. Although the number of university schools and faculties that teach dentistry has increased, and particularly the number of private universities, there is no correlation between their quality and output and the number of places offered on their courses.

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

Lowering bronchoaspiration rate in an acute stroke unit by means of a 2 volume/3 texture dysphagia screening test with pulsioximetry. / Reducción de la tasa de broncoaspiración con el test 2 volúmenes/3 texturas con pulsioximetría en una unidad de ictus.

INTRODUCTION: During acute stroke, 30% of all patients present dysphagia and 50% of that subgroup will experience bronchoaspiration. Our aim was to compare mortality and bronchoaspiration rates associated with the water test compared to those associated with a 2 volume/3 texture test controlled with pulse oximetry (2v/3t-P test) in our stroke unit. PATIENTS AND METHODS: Over a 5-year period, we performed a prospective analysis of all consecutive acute ischaemic stroke patients hospitalised in the Stroke Unit. Dysphagia was evaluated using the water test between 2008 and 2010 (group 0 or G0), and the 2v/3t-P test (group 1 or G1) between 2011 and 2012. We analysed demographic data, vascular risk factors, neurological deficit on the NIHSS, aetiological subtype according to TOAST criteria, clinical subtype according to the Oxfordshire classification, prevalence of dysphagia, percentage of patients with bronchoaspiration, and mortality. RESULTS: We examined 418 patients with acute stroke (G0=275, G1=143). There were significant differences between the 2 groups regarding the percentage of patients with TACI (17% in G0 vs. 29% in G1, P=.005) and median NIHSS score (4 points in G0 vs. 7 points in G1, P=.003). Since adopting the new swallowing test, we detected a non-significant increase in the percentage of dysphagia (22% in G0 vs. 25% in G1, P=.4), lower mortality (1.7% in G0 vs. 0.7% in G1, P=.3) and a significant decrease in the bronchoaspiration rate (6.2% in G0 vs. 2.1% in G1, P=.05). CONCLUSIONS: Compared to the water test used for dysphagia screening, the new 2v/3t-P test lowered bronchoaspiration rates in acute stroke patients.

A consensus statement on the gender perspective in lung cancer.

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

Current diagnosis and treatment of Castleman's disease.

Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment.

SEOM clinical guidelines for the treatment of non-small cell lung cancer (NSCLC) 2015.

Lung cancer is the most common cancer worldwide as well as the leading cause of cancer related deaths as reported by Torre et al (CA Cancer J Clin 65:87-108, 2015]. Non-small cell lung cancer (NSCLC) accounts for up to 85 % of all lung cancers. Multiple advances in the staging, diagnostic procedures, therapeutic options, as well as molecular knowledge have been achieved during the past years, although the overall outlook has not greatly changed for the majority of patients with the overall 5-year survival having marginally increased over the last decade from 15.7 to 17.4 % as reported by Howlader et al. (SEER Cancer Statistics Review 2015).

Follow-up monoclonal gammopathy of undetermined significance in kidney transplant.

OBJECTIVE: The aim of this work was to review the incidence of monoclonal gammopathy of undetermined significance (MGUS) and complications in kidney transplant (KT) patients at the Puerta del Mar Hospital in Cádiz, Spain. This diagnosis was not considered to be a contraindication for transplantation. METHODS: To estimate the incidence of MGUS in KT patients we used the database of our hospital, which included 1,016 patients who received a KT from 1992 to 2012 with a median follow-up of 30 months. The incidence of MGUS in non-transplant patients was estimated from the literature. RESULTS: Out of 1,016 KT patients, 16 developed MGUS; 10 (72.5%) were >50 years old. Two patients developed post-transplantation lymphoproliferative disorders. No cases of progression to multiple myeloma or amyloidosis were seen during immune suppression therapy or after. CONCLUSIONS: MGUS was >100 times more frequent in KT recipients than in the general population (P < .05). But in contrast to MGUS in general population, progression to plasma cell dyscrasia in these patients was absent and its incidence is unknown in KT patients.

Recommendations for radiological diagnosis and assessment of treatment response in lung cancer: a national consensus statement by the Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology.

The last decade has seen substantial progress in the diagnostic and therapeutic approach to lung cancer, thus meaning that its prognosis has improved. The Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology have therefore produced a national consensus statement to make recommendations for radiological diagnosis and assessment of treatment response in patients with lung cancer. This expert group recommends multi-detector computed tomography as the technique of choice for investigating this disease. The radiology report should include a full assessment by the TNM staging system. Lastly, when the patient is on immunotherapy, response evaluation should employ not only response evaluation criteria in solid tumours, but also immune-related response criteria.

[Recommendations for radiological diagnosis and assessment of treatment response in lung cancer: a national consensus statement by the Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology]. / Recomendaciones para el diagnóstico radiológico y la valoración de la respuesta terapéutica en el cáncer de pulmón. Consenso nacional de la Sociedad Española de Radiología Médica y la Sociedad Española de Oncología Médica.

The last decade has seen substantial progress in the diagnostic and therapeutic approach to lung cancer, thus meaning that its prognosis has improved. The Spanish Society of Medical Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM) have therefore produced a national consensus statement in order to make recommendations for radiological diagnosis and assessment of treatment response in patients with lung cancer. This expert group recommends multi-detector computed tomography (MDCT) as the technique of choice for investigating this disease. The radiology report should include a full assessment by the TNM staging system. Lastly, when the patient is on immunotherapy, response evaluation should employ not only Response Evaluation Criteria in Solid Tumours (RECIST 1.1) but also Immune-Related Response Criteria (irRC).

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). TREATMENT: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.