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Background: DT combination has shown efficacy in the adjuvant setting for BRAF-mutated melanoma (BMM) patients (pts) in clinical trials. Previous reports from DESCRIBE-AD resulted in promising overall survival (OS) rates at 12 months. Methods: An observational retrospective study was carried out in 25 GEM sites in Spain. Histologically confirmed and resected BMM pts previously treated with DT according to standard clinical practice in the adjuvant setting were included. Only surgical resection was allowed as a prior treatment to DT. DT discontinuation rate and time to treatment discontinuation were the primary objective. Secondary objectives included safety and efficacy of the combination. Here, we report 3-year results for OS. Results: From 10/2020 to 03/2021, 65 pts were included. Median age was 58 years, 55% were male and 60%, 25%, and 14% had an ECOG PS 0/1/Uk respectively, one patient presented ECOG 3. Allocation of stage IIIA, IIIB and IIIC according to TNM AJCC 7th edition was 29%, 26% and 32%, respectively. There were 3 pts diagnosed at stage I/II but considered of risk, and 2 pts with stage IV but completely resected, all considered for adjuvant DT. Ulceration was present in 40%, Breslow ≥2 mm in 71%, and nodes were microscopically and macroscopically affected in 39% and 22% of pts, respectively. Only 9.2% of pts discontinued DT prematurely due to toxicity and 21.2% had dose reductions to manage toxicity. After a median follow-up of 36.2 m (range: 13-51.1), the overall OS rate at 3-years was 83.5% (95% CI: 74.5-93.5). According to AJCC 7 stage at diagnosis, the 3-years OS rate was 95.2% (95% CI: 86.6-100), 75% (56-100), and 76.8% (60.7-97.2) for stage I-II-IIIA, IIIB, and IIIC-IV respectively. Throughout the study period 11 (16.9%) pts died, of which 10 died due to disease progression and one due to COVID-19 infection. Conclusions: Adjuvant treatment with DT for melanoma achieved good treatment compliance and has proven efficacy in the real world. Adjuvant DT has a clinical impact in survival in line with previous clinical trial COMBI-AD. Editorial acknowledgement: We acknowledge Mfar Clinical Research staff for their assistance in the development of this . Legal entity responsible for the study: Grupo Español Multidisciplinar en Melanoma (GEM). Funding: Grupo Español Multidisciplinar en Melanoma (GEM) as Sponsor with Industry partner NOVARTIS. Disclosure: P. Cerezuela-Fuentes: Financial Interests, Personal, Other, Consultancy, conference,congress attendance/infrastructure: BMS, MSD, Pierre Fabre, Roche, Sanofi, SunPharma. J. Martín-Liberal: Financial Interests, Personal, Other, Lecture fees: Astellas, MSD;Financial Interests, Personal, Other, Lecture fees, advisory fees: Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi;Non-Financial Interests, Personal, Member, membership or affiliation: ASCO, ESMO, SEOM, GEM, EORTC, SOGUG, GEIS. L.A. Fernández-Morales: Financial Interests, Personal, Invited Speaker, Speak at sponsored meetings: BMS, MSD, Pierre-Fabre, Roche;Financial Interests, Personal, Other, Speak at sponsored meetings and advisory role: Novartis. J. Medina Martinez: Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity: Novartis, Roche, Pierre Fabre, BMS, MSD, Sanofi. M. Quindós: Financial Interests, Personal, Other, speaker, consultancy and advisory: AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, Bristol Myers Squibb, Pierre Fabre;Financial Interests, Institutional, Other, Clinical trials: Merck Sharp & Dohme, Roche, Bristol Myers Squibb. A. García Castaño: Non-Financial Interests, Advisory Role: Bristol, MSD, Novartis. T. Puértolas: Financial Interests, Personal, Invited Speaker, Speaker and advisory role: BMS, Novartis;Financial Interests, Personal, Invited Speaker: Roche, MSD, Sun-Pharma;Financial Interests, Personal, Other, Speaker and advisory role: Pierre-Fabre;Financial Interests, Personal, Advisory Role: Sanofi;Financial Interests, Institutional, Other, Clinical trial: Roche, BMS, Apexi en Inc, Aduro Biotech, Alkermes Inc;Non-Financial Interests, Institutional, Other, congresses inscriptions: Lilly, Sun-Pharma, Novartis, Roche, MSD;Non-Financial Interests, Institutional, Leadership Role, Vocal: GEM (Grupo Español Multidisciplinar de Melanoma);Non-Financial Interests, Institutional, Affiliate: SEOM (Sociedad Española de Oncología Médica), GEM (Grupo Español Multidisciplinar de Melanoma). P. Ayala de Miguel: Financial Interests, Personal, Invited Speaker, Public speaking: Novartis, Merck Sharp & Dohme, Sanofi, Pierre-Fabré. B. Campos: Financial Interests, Personal, Other, Speaker or advisory role: Roche, BMS, Sanofi, Novartis, Pierre-Fabre, Sun Pharma;Financial Interests, Personal, Other, Speaker role: AstraZeneca, Merck, ROVI, Leo Pharma. E. Espinosa: Financial Interests, Personal, Advisory Role, Advisory: BMS, MSD;Financial Interests, Personal, Other, Advisory, educational activities: Novartis;Financial Interests, Personal, Invited Speaker, Advisory, educational activities: Pierre Fabre;Financial Interests, Personal, Funding, Funding for translational investigation: Roche;Non-Financial Interests, Personal, Member, Vicepresident: Grupo Español Multidisciplinario de Melanoma. A. Rodríguez-Lescure: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, ROCHE, AstraZeneca, Daiichi Sankyo, Seagen;Financial Interests, Personal, Invited Speaker, Public speaking: Pierre-Fabre;Financial Interests, Institutional, Research Grant, Grant for Clinical Trials: BMS, Lilly, Roche, Novartis, Amgen, Pzifer, Zimeworks, AstraZeneca, G1 Therapeutics, Bayer. L. Espasa Font: Financial Interests, Personal, Full or part-time Employment: Novartis. G. Belaustegui Ferrández: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.
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Background: Many studies have shown benefits of early Palliative Care(PC)in advanced lung cancer patients. There's increasing evidence about better symptom control and survival. A PC physician joined the multidisciplinary LCC last year. Despite the SARS-CoV2 pandemic,472 cases were presented to the LCC in 2020. 470 cases were presented in 2018, so his activity remains stable. Aims: To describe clinical profile of the patients presented to the LCC and early referred to PC. To compare patient's survival when referred from ambulatory setting or when they are admitted in hospital. Methods: Descriptive study.DATA:Age, Gender, Comorbilities, Cancer Histology Tobacco exposure, TNM, Oncology Therapy, Survival time, Barthel, Charlson, Time to first PC consultation. ANALYSIS:T test to compare means of continuous variables and Chi-squared to compare proportions of categorical variables. Kaplan-Meier curve for survival analysis. Results: 41patients of 472(9%) were referred to PC. Males(75%),Median Age 72,87 years old(DS 11,95) no age differences by gender. Current Smokers 25%,Former smokers 65%.Hypertension 70%,Diabetes 45%,Dyslipemia 60%,Heart Failure45%, Renal impairment 35%. Barthel:mean 63,6(DS:22,7) Charlson:mean 6,5(DS2,35) Cancer Histology: Squamous55%, Adenocarcinome35%, Small Cell 7,5%,Other Neuroendocrine2,5%, Disease Stage: StageIV 65%, StageIII 55%, Cancer therapy: Chemotherapy 44%,Radiotherapy 56%, Immunotherapy 30%.PC exclusive follow-up:24,4%, PC and shared follow-up:75,6%. Setting: Refered to Ambulatory PC: 44%, Refered to PC when admitted in an hospital ward: 56%. Time from LCC to PC visit: Ambulatory setting: mean 27,7 days, median 14. Admitted hospital ward: mean 63,14 days(p=0,036), Survival: Ambulatory: mean 142,12 days (DS 90,9), Admitted Hospital ward 59,68 days (DS 59,1)p=0,002. Conclusion: Patients referred from LCC to Ambulatory PC showed an early intervention and better survival profile. Collaboration between LCC and the PC team can improve the early PC support.
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Introduction: There are currently no predictive biomarkers for long-term survival after neoadjuvant chemoimmunotherapy. However, the identification of non-small lung cancer (NSCLC) patients who obtain long-term benefit from chemoimmunotherapy is essential to optimize therapies. Methods: Using samples from NADIM clinical trial (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with nivolumab, we have evaluated the capacity of ctDNA levels before treatment initiation to predict overall survival (OS) and progression-free survival (PFS) by calculating Harrell’s C-statistic and we compare its predictive value with classical survival surrogates as the pathological response and clinical response assessed according to RECIST criteria v.1.1. The ctDNA was analyzed by NGS, using the Oncomine Pan-Cancer Cell-Free Assay™ (Thermo Fisher Scientific®). To explore the prognostic value of the amount of ctDNA at baseline, for each positive plasma sample, we calculated the sum of the mutant allele frequency (MAF) for all detected mutations. Patients who died from COVID19 were excluded from this analysis. Results: In our study, clinical responses based on RECIST criteria were not predictive for OS or PFS. On the contrary, in the multivariate analysis, patients with low ctDNA levels (<1% MAF), in the baseline sample, had significantly improved PFS and OS than patients in whom the opposite situation occurred (adjusted HR: 0.22;95%CI: 0.06-0.75;P=0.016 and adjusted HR: 0.04;95%CI: 0.00-0.45;P=0.008 for PFS and OS, respectively). The adjusted C-statistic (c) to predict PFS for ctDNA was 0.68 (95%CI: 0.51-0.84), which was superior to that of RECIST criteria (c=0.61;95%CI: 0.45-0.78) and similar to that of pathological response (c=0.68;95%CI: 0.52-0.84). Similarly, baseline ctDNA levels predicted OS (c=0.85;95%CI: 0.72-0.99) better than RECIST criteria (c=0.68;95%CI: 0.44-0.93). Conclusion: Pre-treatment ctDNA levels predicted more accurately long-term survival than radiological assessments in NADIM study and might be useful for the design of new clinical trials.
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Introduction: Neoadjuvant chemoimmunotherapy been shown to be highly effective in resectable stage IIIA NSCLC. Now we provide long term survival data Methods: This was an open-label, multicentre, single-arm phase 2 trial in which patients with histologically or cytologically documented stage IIIA NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 and who were deemed locally to be surgically resectable by a multidisciplinary clinical team were treated with neoadjuvant intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6;6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). Here we report progression-free survival (PFS) and Overall survival (OS) at 36 and 42 months, assessed in the modified intention-to-treat population (ITT), which included all patients who received neoadjuvant treatment, and in the per-protocol population (PP), which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Results: Median follow-up time was 37.9 months (95%CI: 36.7-40.7), with a 94% maturity at 36 months. Among the ITT population (N=46), 37 patients, constituting the PP population, received subsequent adjuvant therapy. Of them, 27 (58.7%) patients completed the adjuvant treatment (16 cycles), 10 (21.7%) patients received between 3 and 15 cycles of adjuvant therapy, and 9 (19.6%) patients did not receive adjuvant therapy. At the time of data cutoff (March 2021), progression disease was diagnosed in 14 patients and 9 deaths were recorded in the ITT population. Of these, three deaths corresponded to patients who did not undergo surgery and had disease progression, four deaths corresponded to patients who underwent surgery and had disease progression, and the two remaining deaths corresponded to patients who were diagnosed as being disease free but died from COVID19 infection. Notably, among patients who could not undergo surgery (N=5), one of them is still alive and with no evidence of disease. PFS at 36 and 42 months in the ITT population were 69.6% (95%CI: 54.1-80.7), in both cases. Similarly, PFS at 36 and 42 in the PP population were 81.1% (95%CI: 64.4-90.5) in both cases. The percentage of patients who were alive at 36 and 42 months in the modified ITT population were 81.86% (95% CI: 66.8-90.6) and 78.94% (95%CI: 63.1-88.6), respectively. Likewise, OS at 36 and 42 months in the PP population was 91.0% (95%CI: 74.2-97.0) and 87.3% (95%CI: 69.3-95.1), respectively. Conclusion: The efficacy of nivolumab in combination with platinum-based chemotherapy in patients with resectable stage IIIA NSCLC is clearly supported by long term survival data. Keywords: NADIM trial, neoadjuvant chemo-therapy, long term survival
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Background: Coronavirus disease 2019 (COVID19) is diagnosed by detecting the virus by reverse transcription polymerase chain reaction (RT-PCR). The majority of p go on to develop antibodies (Ab) against viral proteins. However, it is not known how long these antibodies last nor whether cancer treatments could affect the duration of immune response. The prognosis and greater or lesser vulnerability of the oncological population are also unknown. Methods: This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 was carried out in 50 Spanish hospitals. Eligibility criteria was a diagnosis of any thoracic cancer. The first determinations were performed between April 21, 2020 and June 3, 2020, either for p in follow up or in active treatment. Between September 10, 2020, and November 20, 2020, the second antibody (Ab) determination was performed in all previously seropositive p. Clinical and treatment data were collected, as was their clinical situation at study end. Study objectives were to prospectively determine seroprevalence in unselected lung cancer p during the first wave of the pandemic;the natural history of these p;the persistence of immunity more than 4 months after first determination;protection or lack thereof against reinfection after this period, and the nature of such protection;and the influence of treatments on maintenance or loss of immunity. Results: Of 1,500 p studied, 128 were seropositive, representing an overall prevalence of 8.5% seropositivity [95% confidence interval [CI], 7.2%, 10.1%]. Seventy-five percent were in active cancer treatment. COVID-19 infection was suspected in 47.7% [95% CI, 38.8%, 56.6%]. A second determination was performed on average 4.5 months later [IQR: 4;5] and obtained for 104 of the initially seropositive p (81%). A second determination could not be obtained in 24 p, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% (32/104) of p. The severity of the infection, the need for hospitalization (p: 0.032) and the presence of symptoms at diagnosis (p: 0.02), including fever (p: 0.005) and nasal congestion (p: 0.005), were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Ab loss. At time of last follow-up among those p for whom a second determination was performed, 89% (93 p) had completely recovered from the virus, with no lasting after effects. Only 1 of the 128 (0.78%) seropositive p had died from COVID-19. Conclusions: The prevalence of infection in lung cancer p is similar to that of the general population. Immunity against SARS-CoV-2 does not appear to be compromised by treatment, persisting beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population.
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Background: The impact of coronavirus disease 2019 (COVID-19) on cancer patients is still unknown. We aimed to describe the clinical characteristics and 28-day mortality among patients with solid cancers (SC) and COVID-19. Methods: This single-center retrospective study included all adult patients with SC and RT-PCR confirmed COVID-19 between March 12, 2020 and April 30, 2020. Both oncological and COVID-19-related clinical data were collected. COVID-19 severity was defined according to Chinese CDC criteria. In-hospital and 28-day mortality were estimated. Multivariate analysis was adjusted for age, sex and COVID-19 severity. Results: We included 58 (2.7%) of 2130 patients with COVID-19 diagnosed in our hospital;37 (63.8%) were males. Median age was 68.5 years (IQR, 61-75). Main comorbidities were hypertension (28 [48.3%]) and overweight/obesity (23 [39.7%]). Most common SC were prostate (12 [20.7%]), lung (10 [17.2%]) and breast (10 [17.2%]). Overall, 48 (82.8%) patients had previous ECOG PS of 0-1;26 (44.8%) were stage IV and 32 (57.1%) were undergoing cancer treatment. Fifty-six (96.5%) patients were admitted. Most frequent COVID-19 symptoms were fever (40 [69.0%]), cough (35 [62.5%]) and dyspnea (27 [48.2%]). Hydroxychloroquine and azithromycin were used in 40 (69.0%) and 38 (65.5%) patients, respectively;only 3 (5.2%) patients received tocilizumab. Eighteen patients (32.1%) had severe/critical COVID-19. Major complications were respiratory failure (33 [57.9%]), sepsis (14 [24.6%]) and acute kidney injury (13 [22.4%]). Four (6.9%) patients were admitted to ICU. In-hospital and 28-day mortality were 17.2% (10/58) and 24.1% (14/58), respectively. In the multivariate analysis, only dyspnea at diagnosis (hazard ratio [HR]: 6.71, 95% CI 1.40-32.25, p=0.017) and ECOG PS of 2-3 (HR: 4.17;95% CI: 1.13-15.30, p=0.031) were independent risk factors for 28-day mortality. Conclusions: In our patients with SC and COVID-19, 32.1% had a severe/critical disease and 24.1% died within 28 days from diagnosis. Dyspnea at diagnosis and previous ECOG PS of 2-3 were the major predictors for 28-day mortality. Cancer treatment and stage were not associated with mortality. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M. Majem: Honoraria (self), Research grant/Funding (self): BMS;Honoraria (self), Non-remunerated activity/ies: MSD;Honoraria (self), Non-remunerated activity/ies: BOEHRINGER INGELHEIM;Honoraria (self), Non-remunerated activity/ies: ASTRA ZENENCA;Honoraria (self), Non-remunerated activity/ies: KYOWA KYRIN;Honoraria (self): PIERRE FABRE. All other authors have declared no conflicts of interest.