Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

BACKGROUND: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

Clinical course and outcomes of covid-19 in cancer patients: Early result from 'oncovid-19' study

Background: Cancer patients (pts) are considered at higher risk of SARS-CoV-2 infection and more serious COVID-19 illness compared to the general population. We present the early results of the 'onCOVID-19' study exploring clinical course and outcomes of SARS-CoV-2 infection in cancer pts. Methods: In this observational study, we collected clinical data of pts referred to our institution with histologically confirmed diagnosis of solid cancer and COVID-19 from Feb 1 to May 20,2020. COVID-19 diagnosis was laboratory or radiologically confirmed or clinically suspected for suggestive symptoms, including fever (>37,5°C) and/or respiratory tract symptoms, without any other causes. Univariate and multivariate analyses were performed to explore the risk factors associated with severe events defined as hospitalization, admission to an intensive care unit, mechanical ventilation or death. Results: Of the 64 pts enrolled, 35 referring to our Oncology Unit were analysed;the remaining 29, treated for cancer in other institutions, will be included in the analysis after data completion. Pts characteristics: male/female (63/37%), current or former/never smokers (76/24%);stage IV/III (83/17%);median age 63 (47-86) years. Lung was the most frequent site of primary tumor (43%) or metastases (37%). Out 26 (74%) pts on active anti-tumor treatment, 6 (23%) received immune checkpoint inhibitors (ICI). Most common symptoms were fever (40%), shortness of breath (34%) and cough (23%);lymphopenia (<1000/mm3) was found in 5/15 (33%) tested pts. The diagnosis of COVID-19 was only clinical suspected in 2 (6%) cases and confirmed by RT-PCR or imaging (ground glass opacity and/or patchy consolidation) in 11 (31%) and 31 (88%) pts, respectively. An anti-microbial (antibiotics, antiretroviral drugs, plasma therapy) treatment was administrated in 19 (54%) pts;oxygen supplementation was required in 11 (31%) pts. Eleven (31%) pts had severe events, death occurred in 7 (20%) cases. Higher risk for developing severe events was associated with active treatment (RR 4.03, 95%CI 1.8-8.9,p=0.007) and lymphopenia (RR 4.0, 95%CI 1.1-14, p=0.007). Conclusions: Early results of our ongoing study confirmed the vulnerability of cancer pts to COVID-19. Although the small sample size, treatment with ICI and lymphopenia seem to be risk factors for death and severe events. Waiting for final results, screening cancer pts for infection should be advisable before starting immunotherapy or in case of lymphopenia.

Clinical course and outcome of COVID-19 in cancer patients: Early results from the “onCOVID-19” study

Background: Cancer patients are considered at higher risk of SARS-CoV-2 infection and more serious COVID-19 illness compared to the general population. We present the early results of the “onCOVID-19” study exploring the clinical course and outcomes of SARS-CoV-2 infection in patients affected by cancer. Methods: In this observational study, we collected clinical data from patients referred to our institution with histologically confirmed diagnosis of solid cancer and COVID-19 from Feb 1 to May 20,2020. COVID-19 diagnosis was laboratory or radiologically confirmed or clinically suspected for suggestive symptoms, including fever (>37,5°C) and/or respiratory tract symptoms. Univariate and multivariate analyses were performed to explore the risk factors associated with severe events defined as hospitalisation, admission to an intensive care unit, mechanical ventilation or death. Results: Of the 64 patients included, 35 had available clinical data on medical and cancer history required for the analysis. Median age was 63 (47-86) years. Male were 22 (63%) and current or former smokers were 25 (76%). Lung was the most frequent site of primary tumor (15, 43%) or metastases (13, 37%). Out 26 (74%) patients on active anti-tumor treatment, 6 (23%) received immune checkpoint inhibitors (ICI). Most common symptoms were fever (40%), shortness of breath (34%) and cough (23%);lymphopenia (<1000/mm3) was found in 5/15 (33%) tested patients. The diagnosis of COVID-19 was only clinically suspected in 2 (6%) cases and confirmed by RT-PCR or imaging (ground glass opacity and/or patchy consolidation) in 11 (31%) and 31 (88%) patients, respectively. An antimicrobial treatment was administered in 19 patients. Eleven (31%) patients had severe events, death occurred in 7 (20%) cases. Higher risk for developing severe events was associated with active treatment with ICI (RR 4.03, 95%CI 1.8-8.9, p=0.007) and lymphopenia (RR 4.0, 95%CI 1.1-14, p=0.007). Conclusions: We confirmed the vulnerability of cancer patients to COVID-19. Although the sample size was small, treatment with ICI and lymphopenia seem to be risk factors for death and severe events. Screening cancer patients for infection is advisable, in particular before starting immunotherapy or in case of lymphopenia. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Defining COVID-19 outcomes in thoracic cancer patients: TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion)

Background: Patients with thoracic malignancies may have increased risk for COVID-19 mortality. This risk may be attributable to age, comorbidities, smoking history, pulmonary disease burden and cancer-directed therapies. Methods: TERAVOLT is a global consortium examining outcomes and assessing risk factors associated with mortality of patients with thoracic malignancies and COVID-19 infection. Results: As of July 15, 2020, 1012 patients from 20 countries have been entered;median age was 68 with 58 % male, 80% current/former smokers, most common comorbidities of HTN (49%) & COPD (26%);82% NSCLC, 68 % patients with stage IV disease at COVID diagnosis, 65% on treatment (38% chemotherapy, 26% immune checkpoint inhibitor (ICI), 16 % targeted tyrosine kinase inhibitor (TKI). Of these, 72% were hospitalized;56% of patients developed complications, most frequently pneumonia (40%) and 47% who did not have prior oxygen therapy required it. 32% of patients died during their COVID-19 infection. Only 33 % of patients continued their oncology treatment after infection. Patients presenting with pneumonia (OR 2.7 2-3.5), consolidation (OR 2 CI 1,5-2,8), bilateral lung abnormalities (OR 2,8 CI 2-3,9) and pleural effusion (OR 2,7 CI 1,8-4) were at increased risk of mortality. In multivariate analysis age ≥ 65 (OR 1,53 CI 1,11-2,1), active smoking (OR 2 CI 1,3-3), higher stage of cancer (OR 1,9 CI 1,3-2,7), ECOG PS ≥2 (OR 3,7 CI 2,7-5), steroids prior to COVID diagnosis (OR 1,8 CI 1,2-2,7), were associated with increased risk of death, while chemotherapy and TKI therapy use were not and interestingly patients on immunotherapy appeared to be at decreased risk for mortality (OR 0,6 CI 0,5-0,97). Conclusions: Facing this ongoing global pandemic, TERAVOLT is the largest thoracic malignancy database confirming the high risk for COVID-19 mortality in this specific patient group. Physicians need to evaluate the risk of mortality from COVID-19 based on age, smoking status, stage of cancer, performance status, need for steroids and specific therapy in order to determine the appropriateness for cancer therapy and tailor patient care taking into account patients’ wishes and status of pandemic in the country. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: J. Baena Espinar: Advisory/Consultancy: AstraZeneca;Honoraria (self), Travel/Accommodation/Expenses: Angelini. F.R. Hirsch: Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: BMS;Advisory/Consultancy: Merck;Advisory/Consultancy: Daiichi;Advisory/Consultancy: Genentech/Roche;Advisory/Consultancy: Lilly/Loxo;Advisory/Consultancy: Boehringer-Ingelheim. M. Tiseo: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca;Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim;Advisory/Consultancy: Novartis;Advisory/Consultancy: MSD;Advisory/Consultancy: BMS;Advisory/Consultancy: Takeda. E. Felip: Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: AbbVie;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: AstraZeneca;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Blue Print Medicines;Advisory/Consultancy, Advisory role or speaker's bureau: Boehringer Ingelheim;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Bristol-Myers Squibb;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: GSK;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Eli Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Guardant Health;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Janssen;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Medscape;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Merck KGaA;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Spea er's bureau: Merck Sharp and Dohme;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: prIME Oncology;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Springer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Takeda;Advisory/Consultancy, Advisory role or Speaker's bureau: Touchime;Research grant/Funding (self), Research Funding: Fundacion Merck Salud;Research grant/Funding (institution), Research Funding: Grant for Oncology Innovation;Full/Part-time employment, Board (Independent Member: Grifols Boards. H.A. Wakelee: Research grant/Funding (institution), Clinical Research grant: Gilead;Honoraria (self), Advisory/ Consultancy, advisor or consultant honoraria: AstraZeneca;Advisory/Consultancy, Research grant/Funding (institution), advisor or consultant, research: Xcovery;Advisory/Consultancy, advisor or consultant: Jassen;Advisory/Consultancy, advisor or consultant: Daiichi Sankyo, INC;Advisory/Consultancy, advisor or consultant: Helsinn;Advisory/Consultancy, advisor or consultant: Mirati;Advisory/Consultancy, advisor or consultant (not: Takeda;Advisory/Consultancy, advisor or consultant (not: Cellworks;Advisory/Consultancy, Research grant/Funding (institution), advisor or consultant (not: Genentech/Roche;Advisory/Consultancy, Research grant/Funding (institution), advisor or consultant (not: Merck;Travel/Accommodation/Expenses, CME presentation (travel funding): Clinical care options oncology, LLC;Travel/Accommodation/Expenses, CME presentation (travel funding): Fishawack facilitate LTD;Travel/Accommodation/Expenses, CME presentation (travel funding): Medscape;Travel/Accommodation/Expenses, CME presentation (travel funding): Onclive/intellisphere LLC;Travel/Accommodation/Expenses, CME presentation (travel funding): Philips Gillmore Oncology 2018;Travel/Accommodation/Expenses, CME presentation (travel funding): Physician education resource, LLC/MJH;Travel/Accommodation/Expenses, CME presentation (travel funding): Potomac center for medical education;Travel/Accommodation/Expenses, CME presentation (travel funding): Prime Oncology LLC (2018);Travel/Accommodation/Expenses, CME presentation (travel funding): Primo (2018);Travel/Accommodation/Expenses, CME presentation (travel funding): Research to practice;Travel/Accommodation/Expenses, CME presentation (travel funding): UpToDate;Travel/Accommodation/Expenses, CME presentation (travel funding): WebMdHealth;Honoraria (self), Research grant/Funding (institution), honoraria, research funding to: Novartis;Travel/Accommodation/Expenses, International professional society: RGCON- Rajiv gand conference;Travel/Accommodation/Expenses, International professional society: JLCS - japanese lung cancer society;Travel/Accommodation/Expenses, International professional society: KSMO - korean society of medical oncology;Full/Part-time employment, professor of medicine: Stanford university;Travel/Accommodation/Expenses, Scientific advisory committe - travel: ITMIG;Research grant/Funding (institution), research funding to institution: ACEA biosciences. M.C. Garassino: Honoraria (self): Boehringer Ingelheim;Honoraria (self), Local PI, Enrollment in clinical Trials in: Otsuka Pharma;Honoraria (self), Research grant/Funding (institution), PI, Enrollment and Steering: AstraZeneca;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: Novartis;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: BMS;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinic l Trials in: Roche;Honoraria (self), Research grant/Funding (institution), PI, MISP in Thimic malignancies: Pfizer;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: Celgene;Research grant/Funding (institution): Incyte;Research grant/Funding (institution): Inivata;Research grant/Funding (self): Takeda;Honoraria (self), PI, Enrollment in clinical Trials Thimic: Tiziana Sciences;Honoraria (self), PI, Enrollment in clinical Trials in: Clovis;Honoraria (self), PI, Enrollment in clinical Trials in: Merck Serono;Honoraria (self), Research grant/Funding (self), PI, Enrollment in clinical Trials in: Bayer;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: MSD;Honoraria (self), Local PI, Enrollment and Steering: GlaxoSmithKline S.p.A.;Research grant/Funding (institution): Sanofi-Aventis;Honoraria (self), PI, Enrollment in clinical Trials: Spectrum Pharmaceutcials;Honoraria (self), PI, Enrollment in clinical Trials: Blueprint Medicine;Research grant/Funding (institution): Seattle Genetics;Research grant/Funding (institution): Daiichi Sankyo;Honoraria (self), PI, MISP in Thimic malignancies: Eli Lilly. S. Peters: Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: AbbVie;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Amgen;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: AstraZeneca;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Bayer;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Biocartis;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Boehringer-Ingelheim;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Bistrol-Myers Squibb;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium:Clovis;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Daiichi Sankyo;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Debiopharm;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Eli Lilly;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: F. Hoffmann-La Roche;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Foundation Medicine;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Illumina;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Janssen;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Merck Sharp and Dohme;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Merck Serono;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Merrimack;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Novartis;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Pharma Mar;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Pfizer;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Regeneron;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Sanofi;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Seattle Genetics and Takeda;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: AstraZeneca;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Boehringer-Ingelheim;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Bristol-Myers Squibb;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Eli Lilly;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: F. Hoffmann-La Roche;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Merck Sharp and Dohme. L. Horn: Advisory/Consultancy, Consulting: AstraZeneca;Advisory/Consultancy, Consulting: Genentech-Roche;Advisory/Consultancy, Consulting: Incyte;Advisory/Consultancy, Consulting: Merck;Advisory/Consultancy, Consulting: Pfizer;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Consulting and travel to meeting: Xcovery;dvisory/Consultancy, Consulting: EMD Serono;Advisory/Consultancy, Consulting: Tesaro;Advisory/Consultancy, Consulting: AbbVie;Research grant/Funding (self): Boehringer Ingelheim;Research grant/Funding (self), Travel/Accommodation/Expenses, Honorarium: BMS;Honoraria (self), Honorarium: Medscape;Honoraria (self), Honorarium: PER;Honoraria (self), Honorarium: Research to Practice;Honoraria (self), Honorarium: OncLive;Advisory/Consultancy, Consulting: Amgen;Advisory/Consultancy, Consulting: Bayer. All other authors have declared no conflicts of interest.