Background

Phase I CT are a cornerstone in the treatment of cancer patients. Given the future uncertainties due to COVID19 pandemic, one of the concerns is the potential decrease of new phase I CT entering the clinic in subsequent years. Our aim was to evaluate the impact of COVID19 in the Start-up activities of the phase I Unit at Vall d´Hebron Institute of Oncology (VHIO).

Methods

We analyzed the activity of VHIO Clinical Trials Start-Up Unit from 2019 to April 2021. The number of new proposals/studies (NS), pre-selection site visits (PSSV), and site initiation visits (SIV) for phase I CT were analyzed. Specific measures in response to COVID19 pandemic were registered.

Results

Regarding NS, a 9.6% decrease was observed in 2020 in comparison to 2019 (132 vs 146 with an average of 11 NS/month vs 12.16 NS/month respectively). This was mainly due to a decrease during the first wave of COVID19 (Mar -May 2020) with 8.33 NS/month vs 12.66 NS/month in 2019. In 2021 (Jan to Apr), NS increased with an average of 17.25 NS/month. Sponsors were 56.4%Pharma vs 43% Biotech during 2020 and 47.05% vs 52.94% in 2021. Despite the decrease of NS in 2020, an increase of remote PSSV was detected (40 in 2019 vs 60 in 2020). During the first wave of COVID19 we performed an average of 5.66 PSSV/month vs 2.33 PSSV/month in 2019. In 2021, PSSV are still increasing with an average of 6.4 PSSV/month. Forty SIV were performed in 2019, 69 in 2020 and 17 from Jan-April 2021 (average 3.3 SIV/Month, 5.75 SIV/month and 4 SIV/month respectively). On the first wave, 4.33 SIV/month were carried out vs 5 SIV/month in 2019. Remote SIV were performed during COVID19, and hybrid (remote/on-site) during 2021. Documents to explain sponsors the measures undertaken for safe trial implementation have been generated (i.e. remote monitoring, shipment of medication, habilitating COVID free monitoring rooms and treatment wards).

Conclusions

Despite COVID19 and an initial decrease of new studies during 2020, the number of new proposals for phase I CT is increasing in 2021. This appears to be equal for biotech and big pharma proposals. Remote PSSVs are an efficient alternative to on- site visits. Digitalization and measures taken are effective to maintain the Clinical trial start up activity in VHIO and will probably remain after the pandemic is over.

Legal entity responsible for the study

The authors.

Funding

Caixa Research Programe from Caixa Foundation.

Disclosure

C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Exeter Pharma; Financial Interests, Personal, Advisory Board: F. Hoffmann - La Roche Ltd; Financial Interests, Personal, Advisory Board: MediTech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philips; Financial Interests, Personal, Advisory Board: Piere Fabre; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Roche Farma; Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Financial Interests, Personal, Advisory Board: SeaGen; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Gran: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Eli Lilly and Company; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Merck, Sharp and Dhome España S.A.; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Research Grant: Zenith Pharma; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM); Non-Financial Interests, Member: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Member: SOLTI group (Academic research group in breast cancer); Non-Financial Interests, Member: Geicam (Spanish Breast Cancer Research Group); Non-Financial Interests, Member: American Association for Cancer Research (AACR). T. Macarulla Mercade: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL; Financial Interests, Personal, Advisory Board: Advance Medical HCMS; Financial Interests, Personal, Advisory Board: Batxer; Financial Interests, Personal, Advisory Board: BioLineRX Ltd; Financial Interests, Personal, Advisory Board: Celgene SLU; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Genzyme; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: IPSEN Pharma; Financial Interests, Personal, Advisory Board: Lab. Menarini; Financial Interests, Personal, Advisory Board: Lab. Servier; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck, Sharp and Dhome; Financial Interests, Personal, Advisory Board: QED Therapeutics Inc; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Aslan; Financial Interests, Institutional, Research Grant: AstraZecena; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Hallozyme; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merimarck; Financial Interests, Institutional, Research Grant: Millenim; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Pharmacyclics; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Member: American Society of Clinical Oncology - ASCO; Non-Financial Interests, Member: “Sociedad Española de Oncología Médica” – SEOM. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Mersana Therapeutics; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Other, Travel and accommodation: AstraZeneca; Financial Interests, Personal, Other, Travel and accommodation: PharmaMar; Financial Interests, Personal, Other, Travel and accommodation: Roche; Financial Interests, Personal, Advisory Board: Merck Sharps & Dohme de España, SA; Financial Interests, Institutional, Funding: Abbvie Deutschland; Financial Interests, Institutional, Funding: Advaxis Inc.; Financial Interests, Institutional, Funding: Aeterna Zentaris; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Aprea Therapeutics AB; Financial Interests, Institutional, Funding: Clovis Oncology Inc; Financial Interests, Institutional, Funding: EISAI limited LTD; Financial Interests, Institutional, Funding: F. Hoffmann –La Roche LTD; Financial Interests, Institutional, Funding: Regeneron Pharmaceuticals; Financial Interests, Institutional, Funding: Immunogen Inc; Financial Interests, Institutional, Funding: Merck, Sharp & Dohme de España SA; Financial Interests, Institutional, Funding: Millennium Pharmaceuticals Inc; Financial Interests, Institutional, Funding: PharmaMar SA; Financial Interests, Institutional, Funding: Tesaro Inc.; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Faculty Member Gyneacological Track for ESMO 2018 and Chair of Gyneacological Track for ESMO 20: ESMO; Non-Financial Interests, Member: ESMO; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: GCIG; Non-Financial Interests, Member: SEOM; Non-Financial Interests, Member: GOG. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Novartis (AAA); Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag International NV; Financial Interests, Institutional, Invited Speaker: Laboratoires Leurquin Mediolanum SAS; Financial Interests, Institutional, Invited Speaker: Lilly, S.A; Financial Interests, Institutional, Invited Speaker: Medimmune; Financial Interests, Institutional, Invited Speaker: Novartis Farmacéutica, S.A; Financial Interests, Institutional, Invited Speaker: Sanofi-Aventis, S.A. E. Felip: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristrol Meyers Squibb; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Medical Trends; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristrol Meyers Squibb; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dome; Financial Interests, Personal, Invited Speaker: Peervoice; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Springer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Invited Speaker: Touch Medical; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: F. Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Medical Trends; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Peptomyc; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Syneos Health; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Merck Sharp & Dohme Corp; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Daiichi Sankyo Inc; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Exelixis Inc; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Merck KGAA; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Janssen Cilag International NV; Financial Interests, Institutional, Invited Speaker, Clinical Trial: GlaxoSmithKline Research & Development Limited; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Abbvie Deutschland GmbH & Co KG; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Novartis Farmaceutica SA; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Bayer Consumer Care AG; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Takeda Pharmaceuticals International; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Boehringer Ingelheim International GmbH; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Pfizer S.L.U.; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Amgen Inc; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Bristol-Myers Squibb International Corporation (BMS); Financial Interests, Institutional, Invited Speaker, Clinical Trial: Mirati Therapeutics Inc; Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). E. Garralda: Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: F.Hoffmann/La Roche; Financial Interests, Personal, Invited Speaker: Ellipses Pharma; Financial Interests, Personal, Advisory Board: Neomed Therapeutics1 Inc; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Janssen Global Services; Financial Interests, Personal, Invited Speaker: Seattle Genetics; Financial Interests, Personal, Expert Testimony: TFS; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Thermo Fisher; Financial Interests, Personal, Invited Speaker: Bristol-Mayers Squibb; Financial Interests, Personal, Advisory Board: MabDiscovery; Financial Interests, Personal, Advisory Board: Anaveon; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Thermo Fisher; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Taiho; Other, Other, Institutional Travel Grant: Bristol-Mayers Squibb; Other, Other, Institutional Travel Grant: MSD; Other, Other, Institutional Travel Grant: Menarini; Other, Other, Institutional Travel Grant: Glycotope. All other authors have declared no conflicts of interest.

Background

Estrogen receptors (ER), ERα and ERβ, might serve as extra-hepatic regulators of CYP enzymes involved in steroid hormone metabolism such as CYP1B1, 1A1, 2B6, and CYP3A4. The aim of this project was, to study the responsiveness of either ERα negative and ERα positive cell lines on estrogen induced steroid metabolizing CYP enzyme expression, and changes in ERα or ERβ expression.

Methods

Two commercially available human breast cancer cell lines, which either expressed ERα or ERβ (T47D cells, ERα positive, and SKBR3 cells, ERα negative) were cultivated for gene expression analysis with different concentrations of 17-β estradiol (E2) in a range of 100 pM to 1000 nM for 24 hours. ERα protein expression (Isoforms 48 kDa and 66 kDa) was semiquantified by western blot analysis. The influence of E2 on CYP1B1, CYP2B6 and CYP3A4 expression on mRNA level was investigated by qPCR analysis using Lightcycler© realtime PCR technology.

Results

In both cell lines, CYP1B1 expression increased at higher E2 concentrations, but the induction was significant only in the ERα positive cell line. In the ERα positive cell line, CYP2B6 expression significantly decreased with increasing E2 concentrations indicating an inhibitory effect by E2. It was also investigated whether ER expression changes during estrogen exposure of the cells. In the ERα positive cell line, T47D, expression of ERβ, but not that of ERα, significantly increased after incubation with increasing E2 concentrations. In the ERα negative cell line, only ERβ was detected, and no changes in expression occurred after E2 treatment.

Conclusions

We detected differential effects of estrogen on CYP enzyme expression in ERα negative versus positive cell lines. While CYP1B1, the most prominent estrogen metabolizing enzyme showed a tendency to induction in both cell lines, CYP2B6 which is known to be induced by ERα, showed deceased expression levels at higher estrogen concentrations indicating a potential controversial effect mediated by ERβ, since expression of ERβ increased in the ERα positive cell line by estrogen incubation.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

In 2019 Atezolizumab (Atezo) was approved for extended disease small cell lung cancer (ED-SCLC) in combination with cytotoxic chemotherapy by the European Medicines Agency. In the clinical trial IMpower133 only 22 out of 201 patients received prophylactic cranial radiotherapy (PCI) during their treatment with Atezo. No other clinical studies have reported efficacy or safety regarding the combination of radiotherapy (PCI, whole brain radiotherapy (WBR) or consolidating thoracic radiotherapy (TRTX)) with Atezo as single agent or in combination with chemotherapy. In the clinical routine these safety data are urgently needed for treatment decisions of (radio)-oncologists.

Methods

We performed a retrospective data analysis of all patients with SCLC who were treated at the Department of Medical Oncology, Evang. Kliniken Essen-Mitte from January 2019 until April 2021. Patients with combined chemo-/immunotherapy as induction treatment or with immunotherapy as maintenance were compared to those without any immunotherapy receiving similar radiotherapies. If possible pulmonary function before and after pulmonary irradiation was tested. Odds-Ratio for any documented adverse event (AE) and progression-free survival (PFS) for the different groups were calculated.

Results

35 SCLC patients underwent cranial and/or thoracal irradiation (17 patients received both treatments yet). Atezo was administered to 11 of them. 18 Patients received combined chemo-/immunotherapy without any radiotherapy. There were no severe AEs in patients with PCI or WBR regardless of simultaneous administration of Atezo. In patients with TRTX, there was no significant difference in grade I to III AEs. Grade IV AE did only appear in patients without Atezo. A trend towards an improved median PFS was found in patients with TRTX (8.8 months vs. 6.0 months, p=0.062). In five patients, who received TRTX during Atezo maintenance there is preliminary evidence for no deterioration of pulmonary function compared to patients with TRTX without Atezo.

Conclusions

The addition of simultaneous radiotherapy to Atezo-based systemic therapy seems not to be associated with increased toxicity in SCLC patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D.C. Christoph: Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Bayer; Financial Interests, Invited Speaker: Boehringer Ingelheim; Financial Interests, Invited Speaker: Bristol Myers Squibb; Financial Interests, Invited Speaker: Chugai; Financial Interests, Invited Speaker: MSD; Financial Interests, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker: Pfizer; Financial Interests, Invited Speaker: Roche; Financial Interests, Invited Speaker: Sanofi; Financial Interests, Invited Speaker: Takeda; Financial Interests, Writing Engagements: AstraZeneca; Financial Interests, Expert Testimony: AstraZeneca; Financial Interests, Expert Testimony: Bayer; Financial Interests, Expert Testimony: Boehringer Ingelheim; Financial Interests, Expert Testimony: Bristol Myers Squibb; Financial Interests, Expert Testimony: Chugai; Financial Interests, Expert Testimony: MSD; Financial Interests, Expert Testimony: Merck Sharp & Dohme; Financial Interests, Expert Testimony: Novartis; Financial Interests, Expert Testimony: Pfizer; Financial Interests, Expert Testimony: Roche; Financial Interests, Expert Testimony: Sanofi; Financial Interests, Expert Testimony: Takeda; Financial Interests, Speaker’s Bureau: AstraZeneca; Financial Interests, Speaker’s Bureau: Bayer; Financial Interests, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Speaker’s Bureau: Chugai; Financial Interests, Speaker’s Bureau: MSD; Financial Interests, Speaker’s Bureau: Merck Sharp & Dohme; Financial Interests, Speaker’s Bureau: Novartis; Financial Interests, Speaker’s Bureau: Pfizer; Financial Interests, Speaker’s Bureau: Roche; Financial Interests, Speaker’s Bureau: Sanofi; Financial Interests, Speaker’s Bureau: Takeda; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Boehringer Ingelheim; Financial Interests, Advisory Board: Bristol Myers Squibb; Financial Interests, Advisory Board: Chugai; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Merck Sharp & Dohme; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Sanofi; Financial Interests, Advisory Board: Takeda; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Principal Investigator: Merck Sharp & Dohme; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: DGHO; Non-Financial Interests, Member: ESMO; Non-Financial Interests, Member: IASLC. All other authors have declared no conflicts of interest.

Background

TAS-102 is approved for patients with refractory mCRC. It remains to be defined which patients may benefit from this drug in real-life clinical practice.

Methods

Multicenter retrospective observational analysis of mCRC patients receiving TAS-102 in Spanish centers from November 2015 to the present.

Results

222 patients were included. Median age of 62 yr(31-83); 62.6% male. TAS-102 was mostly used in 3º (54.5%), 4º line(29.3%). TAS-102 was very well tolerated. Dose reduction was required in 34.7% but only 4.1% discontinued therapy. Toxicity included neutropenia 74.1%(>G3 20.2%), fatigue 57.8%(G3 5.1%), diarrhea 21.5%(G3 0.5%) and nausea 24.7%(G3 0.9%). Among patients who had SD/PR, 70.7% had neutropenia>G2 with respect to those who did not (p = 0.02). Median of 3 cycles(2-23), median duration of treatment 4.4 months(1.2-26.2), disease control rate(DCR) 33.8% (PR achieved in 1.8%). Median PFS 3.9m (95% CI 3.5-4.2) and median OS 9.3m (95% CI 7.9-10.67). There was no statistically significant difference of PFS/OS according to primary tumor location or RAS/BRAF mutation status, although MMRp tumors was associated with longer PFS (6.1 vs 3.4m, p=0.002) and OS (14.2 vs 6.3, p=0.001). Patients with low-volume metastatic disease(LVMD), defined as no massive hepatic metastasis or simultaneous liver and lung involvement had better DCR than patients with high volume(44,9% vs 24,2%, respectively, p=0.03). PFS (4.1 vs 3.5m, respectively, p=0.024, HR 1.73 95%CI 1.04-1.81) and OS (11.7 vs 7.8m, p=0.012 HR 1.49 95%CI 1.08-2.3) were also significantly better for patients with LVMD. In the subgroup of who received prolonged treatment (>6 cycles;N=51), 43.1% were <65 years, 60.8% had LVMD and 54.9% of patients had received TAS102 as second/third line. Almost all patients in this subgroup (92.2%) presented SD and PFS was significantly higher than in subgroup of patients >5 cycles (9.3 vs 3.36 m, p<0.001, HR 0.15 95%CI 0.1-0.2) and higher OS (15.9 vs 7.46m, p< 0.001, HR 0.35 95%ci 0.24-0.52).

Conclusions

OS and PFS observed in our real-world experience were slightly higher than the RECOURSE trial. In our series, the subgroup with LVMD achieved one of the best rates described in Spanish series. TAS-102 showed a reasonable safety profile.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Incidence of colorectal cancer (CRC) in patients (pts) younger than 50 years (y) or Early-Onset Colorectal Cancer (EO), is rising worldwide. This trend has prompted an earlier initiation age of screening in some countries, and also focused the research on molecular biology of this entity.

Methods

We prospectively enrolled pts with previously untreated metastatic CRC. Blood sample was submitted for comprehensive ctDNA analysis with Guardant360 at baseline (BL) and at tumor progression (P). We described the total number of genetic alterations, Variant Allele Fraction (VAF) and main variants found in two age-of-onset groups: EO (<50 y) and LO (≥50 y).

Results

Of 155 recruited pts, 14 (9%) were EO. In EO group, 14.3% of pts were diagnosed at localised stages (I-III), in contrast with 20.6% in LO. Primary tumors were right sided in 28.6% of EO, and 24.3% of LO. Regarding the number of genetic alterations, we observed a median of 4 per patient at BL and 3 at P in EO, and 5 (BL) and 4 (P) for LO. Median and range of VAF (based on maximum VAF for each patient) was 0.139% (0.013-0.836%) at BL and 0.317% (0.064-0.476%) at P, in EO and 0.149% (0.0005-0.896%) at BL and 0.09% (0.001-0.846%) at P in LO. The genomic landscape showed some differences in prevalent alterations (Table). Among genes with highest VAF in both groups were: APC, TP53, KRAS, SMAD4, PIK3CA, and BRAF. However, in LO we found also NRAS, PTEN, ARID1A and ATM; and in EO, instead, FBXW7, ERBB2, BRCA2 and EGFR. Table. Table: 500P

Genomic alterations with different prevalence (fraction of total alterations) in age based groups

Conclusions

EO pts seem to have some distinct molecular features that can be captured in comprehensive liquid biopsy. The clinical value needs to be further explored.

Legal entity responsible for the study

UGC Intercentros de Oncología Médica. Hospitales Universitarios Regional y Virgen de la Victoria. IBIMA.

Funding

Guardant Health.

Disclosure

J. Alcaide-Garcia: Financial Interests, Personal, Invited Speaker: Amgen; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Roche; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Amgen; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Servier; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Merck; Non-Financial Interests, Personal, Other, Travel and accommodation expenses : Sanofi. M. Benavides: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Institutional, Product Samples: Guardant Health. M. Alvarez: Financial Interests, Personal, Advisory Board: Bristol; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Nanostring. I. Sevilla: Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pharmamar; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: AAA. V. Navarro Perez: Financial Interests, Personal, Invited Speaker: Bristol; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis. M. Kushnir: Financial Interests, Personal, Full or part-time Employment: Guardant Health. I. Faull: Financial Interests, Personal, Stocks/Shares: Guardant Health; Financial Interests, Personal, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.

Background

The immune system plays a central role in the pathogenesis of cancer, inhibiting as well as promoting effects on tumor development. Tumor-infiltrating lymphocytes (TIL) and PD-L1 expression have been described as factors with prognostic influence in the early stages of breast cancer. However, its relationship to other classical prognostic factors of estimated importance is unknown.

Methods

The primary endpoint was to analyse the relationship between the immune profile, characterized by TILs, CD3 and CD8 T lymphocytes and PD-L1, and the histological phenotype and other classical prognostic factors (histological grade, ki67, hormone receptors, HER2 neu). In this way, we analyzed 138 samples from patients with resected early breast cancer at our institution. TILs, CD3 and CD8 T lymphocytes were quantified in the tumor stroma. PD-L1 expression was measured in immune cellularity (IC) and tumor cells (TC) (PD-L1+ if ≥1% and PD-L1- if <1%).

Results

The median of the variables analyzed was: TILs 2% (interquartile range (IQR) 4); CD3 1.6% (IQR 3.95), CD8 1.4% (IQR 3.57). PD-L1 was positive for IC and TC in 40.2% (35/138) and 9.2% (8/138) of patients, respectively. TILs, CD3, CD8 and PD-L1 were significantly associated with G3, Ki67 and negative RE (p <0.05). HER2 phenotype had the highest percentage of TILs (20%, IQR 43.5), CD3 (14%, IQR 23.65) and CD8 (8.4%, IQR 14.7), followed by Triple Negative (TN) (TILs 10% IQR 48.5; CD3 5% IQR 20.8; CD8 2%, IQR 12.8) and luminal type (TILs 1,5% IQR 4; CD3 0.97% IQR 3.8; CD8 0.92%, IQR 3.3). PD-L1_ic expression was higher in TN (PD-L1 ic 3.5%, IQR 25) followed by HER2 (PD-L1 ic 2%, IQR 20) and it had minimal expression in luminal. The expression of PD-L1_tc was significantly higher in HER2 phenotype (PD-L1_tc 0.5%, RQI 1.75) followed by TN (0.5%, IQR 1). Luminal phenotype did not show PD-L1_tc expression.

Conclusions

TILs, CD3, CD8 and PDL1 expressions were significantly associated with worse prognosis phenotypes. HER2 and TN phenotypes presented more TILs and PD-L1 expression than luminal samples. This suggests a greater influence of the immune system in the development of HER2 and TN breast cancer.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Rueda Dominguez: Financial Interests, Institutional, Advisory Role: MERCK; Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Advisory Role: ROCHE; Financial Interests, Institutional, Speaker’s Bureau: MERCK; Financial Interests, Institutional, Speaker’s Bureau: BMS; Financial Interests, Institutional, Speaker’s Bureau: ROCHE; Financial Interests, Institutional, Speaker’s Bureau: TAKEDA. All other authors have declared no conflicts of interest.

Background

Current standard of care for HR+ advanced breast cancer (ABC) uses endocrine therapy (ET) to arrest tumor growth. Unfortunately, most patients eventually develop ET resistance. Activation of the PI3K/AKT/mTOR and CDK4/6 signalling pathways has been linked to ET resistance, leading to combination therapies coupling ET with inhibitors of these signalling pathways. In the phase 3 PALOMA-3 study (NCT01942135), adding the CDK4/6 inhibitor palbociclib to ET with fulvestrant significantly prolonged progression-free survival (PFS). Improved PFS was also observed in the phase 2 FAKTION study (NCT01992952), in which fulvestrant was combined with the potent, selective inhibitor of AKT1, -2 and -3, capivasertib (AZD5363) in aromatase inhibitor-resistant HR+/HER2–ABC patients. Concomitant inhibition of the PI3K/AKT/mTOR and CDK4/6 signalling pathways with ET may further improve clinical benefit and increase the barrier to ET resistance.

Trial design

CAPItello-292 is a phase 1b/3 study to evaluate the safety and efficacy of capivasertib, palbociclib and fulvestrant compared with placebo, palbociclib and fulvestrant in patients with ET-resistant, HR+/HER2– ABC. In phase 1b, up to 72 patients with ABC will be enrolled to identify the recommended phase 3 dose (RP3D) for capivasertib and palbociclib. Cohort 1 will receive capivasertib (320 mg PO BD 4 days on/3 days off for 4 weeks), palbociclib (125 mg PO OD, 3/4 weeks) and fulvestrant (500 mg IM monthly, plus a loading dose in cycle 1 day 15); the primary endpoints are safety and tolerability. In phase 3, up to 628 patients with HR+/HER2− locally advanced (inoperable) or metastatic ABC following recurrence or progression on or after ET will be randomized 1:1 to receive either the RP3D of capivasertib or placebo, plus palbociclib and fulvestrant until disease progression, unacceptable toxicity or withdrawal of consent. The phase 3 primary endpoint is PFS; secondary endpoints include safety, tolerability and overall survival in all patients and PFS in the PIK3CA/AKT1/PTEN-altered subgroup. Enrolment in phase 1b started in April 2021 (NCT04862663).

Clinical trial identification

NCT04862663.

Editorial acknowledgement

We thank Julia SP Mawer, PhD, of Oxford PharmaGenesis, Oxford, UK, who provided medical writing assistance.

Legal entity responsible for the study

AstraZeneca.

Funding

CAPItello-292 is funded and overseen by AstraZeneca.

Disclosure

E. Hamilton: Financial Interests, Institutional, Advisory Role: Pfizer, Genentech/Roche, Flatiron Health, Lilly, Puma Biotechnology, Daiichi Sankyo, Mersana, Boehringer Ingelheim, Cascadian Therapeutics, Elsai; Financial Interests, Institutional, Research Grant: AstraZeneca, Hutchinson MediPharma, OncoMed, MedImmune, StemCentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millenium, TapImmune, Cascadian Therapeutics, Lilly, BerGenBio, Medivation, Pfizer, Tesaro, Kadmon,. G. Schiavon, L.M. Grinsted, E.C. De Bruin, M.T. Catanese: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi Sankyo, Seattle Genetics, Eisai, Macrogenics, Sermonix, Immunomedics, and AstraZeneca; Financial Interests, Personal, Other, Honoraria: Samsung, Mylan and Puma.

Background

Influenza virus and S. pneumoniae infections in cancer patients (pts) are responsible of a higher morbidity and mortality rates. Limited data are available about safety, efficacy, immunogenicity and timing of influenza (I) and pneumococcal (P) vaccine (vax) in pts receiving active treatment. However, I and P vax in cancer pts and their family members (FMs) are reccomended.

Methods

This is a single institution prospective study conducted at L. Sacco Hospital (Milan, Italy) between Sept 20 and Apr 21. The aim was to assess efficacy and safety of vax. Cancer pts, age>18yo, in active antineoplastic treatment and FMs age>18yo were included. Each pt received I+P vax on the same day of therapy. Any local and systemic Adverse Event (AE), episode of Influenza Like Illness (ILI), pneumococcal infection (PI), access to Emergency Department (ED) or Hospital admission (HA) and delay of therapy (DoT) were recorded. The frequency of AEs, ILI episodes and PI among pts and age- and gender- matching FMs were compared.

Results

194 pts (63y median age, 67.5% female) and 140 FMs (59y median age, 49% female) were enrolled. CANCER: 92% solid and 8% hematological malignancy, 69% metastatic stage. TREATMENTS: 54% ≥1 previous line of therapy; 38% chemotherapy, 31% target, 17% chemo+target, 14% hormone therapy. VAX: I-vax received for first time in 47% pts and 72% FMs. 100% pts and 49% FMs received I+P-vax. LOCAL AEs: I-vax: 34% pts and 19.6% FMs (p=0.01). P-vax: 35.7% pts and 20.7% FMs (p=0.11). The most common was pain in site of injection. SISTEMIC AEs: 19.6% pts and 8.5% FMs (p=0.11); the most frequent was fatigue. EFFICACY: ILI were recorded in 8.8% pts (3 had a HA and 1 a DoT) and 3.6% FMs (p=0.04). No PI was recorded. In a logistic regression analysis type of therapy, previous treatment and the use of steroid don’t significantly impact on vax safety and efficacy.

Conclusions

Few ILI events were observed due to vax and probably to all measures adopted to prevent SARS-CoV-2 virus spread. Except for local I-vax AEs, no differences were observed in efficacy and safety between the 2 groups. During the observation time, >70% of cancer pts in active treatment received I and P vax, so the vaccination coverage was achieved, reducing the pressure on territorial healthcare system.

Clinical trial identification

Trial protocol n. 2020/ST/433 release by Local Ethic Committee.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.M. La Verde: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: Gentili; Financial Interests, Institutional, Funding: EISA. D. Dalu: Financial Interests, Personal, Invited Speaker: Gentili; Financial Interests, Personal, Other: MSD. A. Riva: Financial Interests, Personal, Other: MSD,; Financial Interests, Personal, Other: ViiV; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Janseen; Financial Interests, Personal, Other: Cilag. S. Antinori: Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Merck. M. Galli: Financial Interests, Personal, Other: ViiV; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AbbVie; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Janssen; Financial Interests, Personal, Other: Roche. All other authors have declared no conflicts of interest.

Background

The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly in making timely cancer diagnosis. Our public health system has been concerned about potential delays leading to a higher proportion of patients with advanced stages. Our cancer diagnosis fast-track program (CFP) in the Clinic-Malvarrosa Health department in Valencia (Spain) is connecting primary care (PC) with different specialists to speed cancer diagnosis and treatment upon well founded suspicion. A 10-year evaluation of our CFP has recently been published. The aim of this analysis was to investigate the impact of the COVID-19 pandemic on the CFP.

Methods

We analysed the programme flow during the state of emergency starting on March 16, 2020 for one year.

Results

During that year, 975 suspected cancer cases were submitted to the CFP. The submissions only decreased during the times of highest COVID-19 incidence and stricter lockdown (March, April and October 2020). However, referrals were slightly higher than in the two previous years (average 877). Of those 975 patients, 817 were seen by the corresponding specialist. A cancer diagnosis was confirmed in 197 (24.1%) with 33% urological, 23% breast, 16% gastrointestinal and 9% lung cancer. Median time from referral to the specialist visit was 13 (interquartile range, 8 to 22 days) days and a diagnosis was reached in a median of 18 days (interquartile range, 10 to 30 days). In cancer patients, treatment was started in around 30 days (interquartile range, 13.5 to 51 days) from the time of diagnosis. Sixty-one percent of cancers were found in an early stage, 20% in a locally advanced stage, and 19% in an advanced stage. These intervals and proportions were similar to the previous years.

Conclusions

Our programme has proven to be a reliable tool to help PC physicians referring patients with cancer suspicion cancer, maintaining its normal flow and efficacy despite the current pandemic.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Large cell neuroendocrine lung carcinoma (LCNEC) is an aggressive subtype with an incidence around 3% of all lung cancer. The treatment approach for advanced patients remains controversial due to the lack of large randomized trials including this subtype. Owing to this fact, molecular characterization using next generation sequencing (NGS) technology has become a key tool for the molecular profiling of LCNEC.

Methods

We performed a retrospective analysis of 55 patients with LCNEC treated in our institution from 2011 to 2020. Clinical characteristics and molecular alterations were described. Different NGS platforms were used.

Results

Of 55 patients analyzed, NGS was performed in 25 (tissue NGS in 52%, blood based NGS in 24% patients, both in 24%). Up to 71% of patients were male and all of them heavy smokers. The initial stage diagnosis was III for 22,6% and stage IV for 55% of patients. Most cases were pure large cell neuroendocrine tumors (87%), followed by combined histology with adenocarcinoma (13%). 49 % of patients had KI- 67 labeling index ≥ 50 %. PD-L1 status using IHC 22C3 pharmDx was performed in 59% of tumor samples (PD-L1<1% 56,6 %, PD-L1 1-49% 26,6% PDL1≥50% 16,6%). Tumor mutational burden was ≥10 mut/Mb) in 3 out of 4 patients evaluated. TP53 mutation was the most common molecular finding (52%). From the 11 patients with TP53 wild type, 9 had mutations in other genes (45.4% KRAS, 9% FGFR-1, 9% ERBB-2, 9% PI3K and 9% RET rearrangement), stablishing a hypothetical higher dependance on oncogenic activation. Moreover, mutations in SWI/SNF chromatin-remodeling complexes were also detected (SMARCA4 8% and ARID1A 8%). Other mutations were detected in 14 patients (56%): KRAS (32%), EGFR (8%), BRAF (4%), ERBB2 (4%), BRCA1 (4%) and DDR2 (4%), with potential clinical significance.

Conclusions

Comprehensive molecular tumour profiling allows to identify specific mutations which can be targeted by approved treatments or by new drugs under development in clinical trials in order to improve the poor prognosis of these patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Garrido Lopez: Financial Interests, Personal, Advisory Board: abbvie; Financial Interests, Personal, Advisory Board: amgen; Financial Interests, Personal, Invited Speaker: astrazeneca; Financial Interests, Personal, Advisory Board: bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Gebro; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board, Spouse: Nordic; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Other, Local PI: Apollomics; Financial Interests, Institutional, Other, Local PI: Array Biopharma; Financial Interests, Institutional, Other, Local PI: Blue Print; Non-Financial Interests, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Borad member: AECC; Non-Financial Interests, Leadership Role, Council member as Women for Oncology Committee Chair Fellowship and Award Committee and Press Committe Faculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Leadership Role, President of the Spanish Federation of Medical Societies (FACME): FACME; Non-Financial Interests, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASCL; Non-Financial Interests, Leadership Role, Former President of Spanish Medical Oncology Society Member of the Spanish National Health Advisory Board: SEOM. All other authors have declared no conflicts of interest.

Background

Malnutrition is frequent, but usually under-recognised in aNSCLC. Pre-treatment nutritional status is an important prognostic factor in aNSCLC patients (pts). However, its value is not yet clarified in those receiving targeted therapies, including tyrosine kinase inhibitors (TKIs). The aim of the present study was to define an algorithm for early identification of malnourished pts with oncogene-addicted aNSCLC.

Methods

In 49 aNSCLC oncogene-addicted pts (EGFR mutated or other as ALK, ROS1, BRAF mut), a nutritional screening was performed before starting TKIs therapy. Body mass index (BMI; kg/m²), handgrip strength (kg), previous 6-months weight changes (%), albumin levels (g/dl) and Prognostic Nutritional Index-PNI (10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm³) were collected). Correlations between the nutritional parameters and the clinicopathological characteristics were analysed using Student’s t-test.

Results

Patients’ characteristics were as follows: median age (range) 67 y (35-84); male/female 12/37; EGFR/ALK/ROS1/BRAF addiction 32/8/6/3; BMI ≤18.5/18.5-24.9/>25 3/32/14. Focusing only patients with normal BMI (18.5-24.9, G1) vs those with high BMI (>25, G2), mean (SD) handgrip strength was 22.8 kg (6.8) vs 28.2 kg (11.1) (p=0.05); mean 6-month weight change was -4.1 kg (6.5) vs +7.2 kg (12.1) (p<0.001); mean albumin levels were 3.5 (0.5) vs 3.2 g/dl (0.4) (p=0.05); mean Prognostic Nutritional Index (PNI) score was 34.9 (5.3) vs 31.7 (3.6) (p=0.05). Grouping pts according to tumor mutation (EGFR vs other), mean BMI was 22.3 (4.1) vs 25.4 (6.3) (p=0.04); mean 6-months weight change was -3.5 kg (9.5) vs +3.4 kg (10.2) (p=0.02). Pts with mutation other than EGFR presented more frequently BMI >25: 9/15 (60%) vs 5/31 (16.1%) (p=0.01). Pts with BMI>25 presented higher functional index (handgrip), higher 6-month weight gain and were less frequently EGFR mutated. Furthermore, they had lower albumin levels and PNI scores.

Conclusions

According to our preliminary data, aNSCLC oncogene-addicted pts with BMI>25, despite having higher functional indexes, had worse nutritional parameters and may benefit from full nutritional assessment and counselling to prevent sarcopenic obesity.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Capelletto: Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Advisory Board: MSD. M.L. Reale: Other, Institutional, Advisory Board: Eli Lilly; Other, Institutional, Advisory Board: Boehringer Ingelheim. M. Tampellini: Other, Speaker’s Bureau: Merck; Other, Advisory Board: Amgen; Other, Speaker’s Bureau: Sanofi; Other, Advisory Board: MSD; Other, Speaker’s Bureau: Servier. S. Novello: Other, Advisory Board: AstraZeneca; Other, Advisory Board: Boehringer Ingelheim; Other, Advisory Board: BeiGene; Other, Advisory Board: Eli Lilli; Other, Speaker’s Bureau: Takeda; Other, Expert Testimony: Pfizer; Other, Expert Testimony: Roche; Other, Speaker’s Bureau: Amgen; Other, Speaker’s Bureau: Sanofi; Other, Speaker’s Bureau: BMS; Other, Expert Testimony: MSD. All other authors have declared no conflicts of interest.

Background

Death at home is an increasingly more common measure for improving the quality of palliative care services. The study analyzes the factors that may influence the place of death of oncology patients in palliative care (hospital/home), focusing on clinical characteristics.

Methods

Study design: longitudinal, prospective single-cohort, analytical. 427 people were studied in 2018 in the Bahia de Cadiz-La Janda District (Andalusia, Spain). Data were collected during initial evaluation, follow-up, Last Days and Hours of Life (LDHL) and after death. Among the data gathered: place of death, Palliative Performance Scale (PPS), Palliative Care Complexity Index (IDC-Pal), Charlson Comorbidity Index (CCI), hospital admissions, advanced treatments and symptoms during follow-up and LDHL.

Results

52.2% of patients died at home and 47.8% died in the hospital. Among the individuals who died at home, the results reveal: - A less complex situation (IDC-Pal) throughout the entire process (60.9%, 84.1% and 88.4%; p<0.02 in all these cases). - Less prognosis of survival at initial evaluation (PPS) (57.2 vs 52.4; p=0.003). - Absence of hospital admissions (26.8% vs 78.6%; p<0.001) or a lower number of admissions (0.32 vs 1.12; p<0.001). - Absence of toxicity to opioids (p=0.05), as well as lower pain intensity during LDHL (3.45 vs 4.31; p=0.01), dyspnea (2.94 vs 3.89; p=0.009), nausea/vomiting (1.31 vs 1.72; p=0.031) and anxiety (4.31 vs 5.10; p=0.030). No significant differences were found in place of death (home/hospital) according to age, sex, advanced complementary treatment and other symptoms/complications studied.

Conclusions

The main clinical characteristics that have been found to influence the place of death are: case complexity, survival prognosis, hospital admissions and number of admissions during the process, toxicity to opioids, and intensity of certain symptoms in LDHL, such as: pain, dyspnea, nausea/vomiting and anxiety. It is essential to conduct a thorough evaluation of this type of patient and process, but it may prove especially important to prioritize the aspects herein identified.

Legal entity responsible for the study

The authors.

Funding

Biomedical Research and Innovation Institute of Cádiz (INiBICA). Project subsidized within the framework of the Integrated Territorial Initiative (ITI) 2014-2020 for Cádiz by the Andalusian Consejería de Salud and by the European Regional Development Fund (FEDER).

Disclosure

All authors have declared no conflicts of interest.