Background

Adenosine A2a receptor (A_2AR) blockade in combination with anti-programmed death-1 (PD-1) antibody (Ab) may alleviate immune-suppression, reduce tumor growth, and increase antitumor activity of anti-PD-1 Ab. Taminadenant (A_2AR antagonist) +/- spartalizumab (anti-PD-1 Ab) has preliminary antitumor activity in a Ph Ib study in non-small cell lung carcinoma. We present results of taminadenant + spartalizumab in a Ph II study in MSS CRC (NCT03207867).

Methods

In Part I of the study, pts with MSS CRC were treated with 160 mg oral taminadenant twice daily continuously + 400 mg intravenous spartalizumab every 4 weeks. The primary objective was to evaluate efficacy, using overall response rate (ORR by RECIST v1.1). Disease control rate (DCR) is the proportion of complete response, partial response (PR), or stable disease (SD). Following an interim analysis after the initial 14 evaluable pts with MSS CRC, 40 additional pts were enrolled in two groups: RAS-wildtype (WT) and RAS-mutant (Mt). Tumor biopsies were taken pre- and on-treatment.

Results

As of 20 Nov 2020, 58 pts with MSS CRC were enrolled (RAS-WT: n=27; RAS-Mt: n=29; RAS-Unknown [Uk]: n=2); demographics were similar across cohorts. The majority (69%) of pts had received ≥3 lines of prior therapy. Of 58 pts, 1 (2%) had a PR (Mt: n=1), 11 (19%) SD (WT: n=7; Mt: n=4), 34 (59%) progressive disease (WT: n=16; Mt: n=16; Uk: n=2), and 12 (21%) response unknown (WT: n=4; Mt: n=8). Of the pts with SD, 5 showed tumor shrinkage (WT: n=4; Mt: n=1); 4 had response for >6 months and 1 discontinued treatment due to an adverse event (AE). ORR was 2% (95% CI: 0.0–9.2), and DCR was 21% (95% CI: 11.2–33.4). Of 58 pts, common all-grade (G) treatment-related AEs ([TRAEs]; ≥15% pts) were fatigue (21%) and decreased appetite (16%); ≥G3 TRAEs (≥5% pts) were aspartate/alanine aminotransferase (5/9%) or lipase (5%) increase. Pharmacokinetics and biomarker data will be presented.

Conclusions

Efficacy results of taminadenant + spartalizumab showed 5 pts obtained clinical benefit (1 PR and 4 sustained SD with tumor shrinkage), with no difference in response between RAS-WT and RAS-Mt. Taminadenant + spartalizumab was well tolerated in pts with MSS CRC.

Clinical trial identification

NCT03207867: Protocol number: CNIR178X2201; release date: October 22, 2020.

Editorial acknowledgement

Writing and editorial assistance was provided by Heather Latimer of ArticulateScience, UK.

Legal entity responsible for the study

Novartis Pharmaceutical Corporation.

Funding

Novartis Pharmaceutical Corporation.

Disclosure

O. Saavedra Santa Gadea: Financial Interests, Personal, Other, Travel, accommodations, expenses: MSD, Kyowa Kirin. R. Greil: Financial Interests, Personal, Advisory Role, Honoraria, research funding, travel and expenses: Celegne, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Janssen. M.J.A. de Jonge: Financial Interests, Personal, Advisory Board: Faron Pharmaceuticals Ltf. D. Tan: Financial Interests, Personal, Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: Pfizer, Boehringer Ingelheim, Roche; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb, Takeda, Novartis, Roche, Pfizer; Financial Interests, Institutional, Funding, Research Funding: Novartis, GlaxoSmithKline, AstraZeneca. G. Jerusalem: Financial Interests, Personal, Other, outside the submitted work: Novartis; Roche; Pfizer; Lilly; Amgen; BMS; AstraZeneca; Daiichi Sankyo; AbbVie; Financial Interests, Institutional, Research Grant, outside the submitted work: Roche; Novartis; Pfizer; Non-Financial Interests, Other, outside the submitted work: Novartis; Roche; Pfizer; Lilly; Amgen; BMS; AstraZeneca; Medimmune; MerckKGaA. P. Grell: Financial Interests, Personal, Advisory Role, Consulting fees: Roche, Servier; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: Roche, Servier; Financial Interests, Institutional, Funding, Research Funding: Novartis. Z. Wainberg: Other, Personal, Other, Honoraria: Amgen; AstraZeneca; Daiichi; Bayer; BMS; Merck; Ipsen; Five Prime; Gilead; Arcus; Astellas; Molecular Templates; Array; Other, Advisory Role: Amgen; AstraZeneca; Daiichi; Bayer; BMS; Merck; Ipsen; Five Prime; Gilead; Arcus; Astellas; Molecular Templates; Array; Financial Interests, Institutional, Research Grant: Amgen; AstraZeneca; Daiichi; Bayer; BMS; Merck; Ipsen; Five Prime; Gilead; Arcus; Astellas; Molecular Templates; Roche/Genentech; Array/Pfizer. J. Wolf: Financial Interests, Personal, Advisory Board, Advisory Board and Lecture Fees: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Institutional, Funding: BMS, Janssen Pharmaceutica, Novartis, Pfizer. M.S. Carlino: Financial Interests, Personal, Advisory Role: Amgen; BMS; Eisai; Ideaya; MSD; Nektar; Novartis; Oncosec; Pierre-Fabre; Qbiotics; Regeneron; Roche; Sanofi; Financial Interests, Personal, Other, Honoraria: MSD; BMS; Novartis. S. Kasper: Other, Personal, For conducting studies: Novartis; Other, Personal, For conducting clinical trials: BMS; Roche; Financial Interests, Personal and Institutional, Research Grant, For conducting clinical trials: BMS; Roche; Financial Interests, Personal, Other: Amgen; Sanofi Aventis; Financial Interests, Personal and Institutional, Research Grant, For ISTs: Lilly; Merck Serono; Servier. T.A. Yap: Financial Interests, Institutional, Research Grant: Artios, AstraZeneca, Bayer, Clovis, Constellation, Cyteir, Eli Lilly, EMD Serono, Forbius, F-Star, GlaxoSmithKline, Genentech, ImmuneSensor, Ipsen, Jounce, Karyopharm, Kyowa, Merck, Novartis, Pfizer, Ribon Therapeutics, Regeneron, Repare, Sanofi, Scholar. J. Otero: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares, Employee of Novartis: Novartis. X. Yang: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis: Novartis. V. Nesbitt: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis: Novartis; Financial Interests, Personal, Stocks/Shares, RSUs: Novartis. J. Kim: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. L. Ho Lee: Financial Interests, Personal, Full or part-time Employment: Novartis. S. Choudhury: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis: Novartis. T.A. Leal: Financial Interests, Personal, Advisory Board: Takeda, Blueprint, Janssen; Financial Interests, Personal, Advisory Board: BMS, Jazz Pharmaceuticals, EMD Serono; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BeyondSpring, InvisionFirst; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Bayer, Merck; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: Novocure, Daiichi Sankyo, Lilly. All other authors have declared no conflicts of interest.

Background

There is conflicting data that breast conservative surgery (BCS) is associated with higher locoregional recurrences (LRR) than mastectomy in young breast cancer patients (BCY). However, there is little data from the African population.

Methods

Women aged ≤40 with stage I-III BC, diagnosed in 2008 - 2017 in two Alexandria centres, Egypt, were retrospectively reviewed. We compared the clinicopathological characteristics, treatment, LRR and local recurrence-free survival (LRFS) between patients who underwent mastectomy vs BCS.

Results

Out of the nine hundred and twenty patients included in this analysis, 33% (307) underwent BCS. The mean age at diagnosis was 35.15 years (SD ± 4.3) and was similar in both groups. The table summarises the clinicopathological characteristics of the mastectomy and BCS group. The patients who underwent mastectomy had significantly more T3/T4 tumours and positive lymph nodes (N+), while those who underwent BCS had more grade 3 tumours. The receptor expression (ER, PR, HER2), Ki-67 and the timing of chemotherapy were comparable across the groups. All the BCS patients were irradiated, whereas, in the mastectomy group, T3/T4 and/or N+ patients were irradiated. After a median follow up of 41 months (Range: 1-143), the LRR was similar in both groups: 10% (61) in the mastectomy group and 12% (38) in the BCS group; p=0.263. There was no significant difference in the mean LRFS between the two groups, 124 vs 112 months in mastectomy and BCS groups, respectively; HR 0.835 (95% CI: 0.557 – 1.253, p=0.383). Table: 163P

Clinicopathological characteristics and treatment of the mastectomy vs BCS

Conclusions

To our knowledge, this is one of the largest studies of young breast cancer patients in Africa comparing the local failure after mastectomy and BCS. In this large study, breast-conserving surgery was not detrimental to locoregional control in young African breast cancer patients and should be considered whenever feasible and discussed with patients for a joint decision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Invasive lobular carcinoma (ILC) is increasingly recognized as a unique breast cancer histological subtype. We aimed to determine the incidence and clinicopathological characteristics of young breast cancer patients.

Methods

We retrospectively reviewed the records of female patients aged ≤40 diagnosed with lLC, both classic ILC and mixed invasive lobular-ductal carcinoma (ILC-IDC), between 2008 and 2017 in two centres in Alexandria, Egypt. We determined their incidence and clinicopathological characteristics.

Results

Out of the 1228 patients, 4.4% (n=54) were diagnosed with invasive lobular carcinoma, in which 29 out 54 were classic ILC (54%). The median age at diagnosis was 37 years (Range: 24 – 40 years), and 25% had a positive family history of BC. The majority of the patients underwent MRM (82.4%), and nearly a quarter (13.7%) had a multifocal disease. The mean tumour size was 4.4 cm ±2.1, while positive axillary lymph nodes were 6.7±7.7, with TNM stage III being the most common – 64%. All patients had grade 2 tumours. The lymphovascular invasion was present in 65% of the patients. Nearly half (48.6%) had an extracapsular extension. Almost all patients had estrogen/progesterone receptor-positive tumours (97.8%). At a median follow up of 28 months (Range: 2 – 135), 41% of the patients (n=22) developed recurrences. 77% out of the 22 relapses were distant recurrences. The median disease-free survival was 36 months (95% CI: 30.1 – 41.9).

Conclusions

Invasive lobular carcinoma is infrequent in young breast cancer patients. Our results confirm that ILC tumours are frequently intermediate grade and almost exclusively hormone-receptor-positive, even in young breast cancer patients. Distant relapses are the most common, despite the short follow-up.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The range of cardiovascular risks in cancer patients is diverse. Patients with metastatic/distant illness at the time of diagnosis have the highest standard mortality rate of fatal heart attack than do regional and localized staged patients. We wanted to investigate the pattern of distant sites (bone, brain, liver, and lung metastases) and subsequent survival of patients with heart-related deaths from all cancer forms.

Methods

We conducted a Surveillance, Epidemiology, and End Results (SEER) registry-based investigation (2010-2016) and collected data on cancer patients with advanced stages who died from cardiac events. For survival analysis, the Kaplan-Meier technique was used, and a multivariate model was created by controlling for multiple confounding factors.

Results

We extracted 6021 distant cancer patients who experienced fatal heart death. Distant lung cancer was predominantly seen with a higher percentage of fatal heart attack rate than orodigestive tract and bone marrow (33.7%, 19%, 16.2%). In the study difference of survival between the metastatic sites in lung, the liver metastasis reveals worse survival than others (p=>0.0001; median months: 2 vs. 1 month). Further adjusted variables by multivariate model, the lung metastases showed favorable survival than liver mets site (P=<0.000, 1.395(1.244-1.564).

Conclusions

Most cases of metastasis in heart-specific death patients were reported in lung cancer sites. While liver metastasis was associated with worse prognosis, the metastasis to lung was related to greater survival than other metastatic locations. More research is needed to predict the prognosis of distant patients and the related cardiac morbidity and mortality.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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

There are not specific information about otucomes of COVID-19 infection in patients with breast cancer. We aimed to describe the outcomes in this population in our national cohort of patients with cancer and infection for COVID-19.

Methods

ACHOCC-19B registry is a multicenter observational study composed of a cross-sectional and a prospective cohort component. Eligibility criteria were the diagnosis of breast cancer and COVID-19 infection confirmed with RT-PCR. Follow-up of 30 days was completed. Clinical data were extracted of the multicentric register of cancer and covid-19 in Colombia (ACHOCC-19), collected from Apr 1 until Oct 31, 2020. The primary outcome was 30-day mortality from all causes and secondary outcome was asymptomatic disease. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using multivariable logistic regression.

Results

132 patients were included(18,5% of global ACHOCC-19 cohort). 18,2% died and 25,8% was asymptomatic. In relation to the patients who died vs did not died, 68 vs 66% were > 50 years, 20 vs 10,2% with obesity, 32 vs 51,4% without comorbidities: 24 vs 12% with Diabetes, 56 vs 29% arterial Hypertension, 17,75 vs 3.88% ECOG >2, 50 vs 12,5% progressive cancer, 20 vs 5,6% bacterial coinfection, 65 vs 25,2% received antibiotic and 68 vs 19% steroids for Covid-19 infection. 11.3% had severe infection and received ventilatory support and 66% died. About the asymptomatic patients 74% were > 50 years, 2,9% had obesity, 56% without comorbidities, 56% with ECOG 0 and 17,6% had metastatic disease. In the logistic regression analysis, age > 50 years (OR 2,7 95% 0,54-13,81), >2 comorbidities (OR 3,48 95% 0,26-45,71), progressive disease (OR 3,52 95% 0,47-26,57), steroids (OR 6,62 95% 1,5-26,6) and antibiotic treatment for Covid19 (OR 6,88 95% 1,60-29,76) behaved as a risk factors for mortality, but only steroids and antibiotic was statistically significant.

Conclusions

In our study, breast cancer patients have high mortality by Covid-19 infection. Age, comorbidities, ECOG >2, progressive disease, and use of antibiotic and steroids are factors for worse prognosis.

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 Chile, lung cancer is the second leading cause of cancer-related death. Most diagnoses are made in an advanced stage, with one third of all NSCLC cases in stage III unresectable disease, with a 5-year OS of 15%. The current standard of care for these patients has been platinum-based doublets with concurrent radiation therapy in combination with immunotherapy (IO).

Methods

We have performed a retrospective review over 517 clinical records of patients who were treated between 2014 – 2019 at “Instituto Nacional del Tórax”. Baseline clinical characteristics as well as therapy indicated and toxicity were recorded. Outcomes were analyzed by measuring progression free and overall survival. Toxicity was assessed by CTACAE v5.0 and response to treatment by RECIST 1.1 criteria.

Results

54% of the patients were men. 68% were in ECOG 0 performance status and 32% in ECOG 1, with a mean BMI of 26 kg/m2. All patients were smokers and 71% had some comorbidity in their medical history. 74% of NSCLC were adenocarcinomas and 26% squamous cell variant. 23% were stage IIIA, 54% IIIB, and 23% IIIC. Only 6 patients received adjuvant treatment before progressing to stage III disease. 86% received cisplatin (median 54.4 mg, range 40 to 60 mg) as a single dose combined with standard radiotherapy of 60 Gy averaged in 30 fractions in a concurrent modality in 91% of cases. 50% received durvalumab as maintenance. G3 toxicities were reported in 19.4%, corresponding to nausea and actinic pneumonitis. G2 toxicities were 37.1% for actinic pneumonitis and 11.4% for esophagitis. No grade 4 and 5 toxicities were reported. 82.8% progressed at 15 months on average and 17% maintained stable disease. The ORR was 77.1% among responders, the mOS was 23 months (95% CI [3.21-16.7]), and the mPFS was 10 months (95% CI [8.25- 11.75]).

Conclusions

Management of locally advance unresectable NSCLC has been changed since PACIFIC trial was published. Unfortunately, Public Health Insurance Systems does not cover access for IO. This local study was an attempt to demonstrate that classic concurrent CRT in medium-income countries could still have a relevant role in management.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. María Paz: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche. F. Orlandi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Research Grant: Astellas Pharma; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Research Grant: Sanofi. All other authors have declared no conflicts of interest.

Background

Soto, a specific, irreversible KRAS^G12C inhibitor, has monotherapy clinical activity in KRAS p.G12C-mutated solid tumors, with an objective response rate of 7.1% for heavily pretreated CRC in the CodeBreaK 100 phase I trial. KRAS^G12C blockade can lead to accumulation of activated EGFR. Combining Soto with an EGFR inhibitor may produce synergistic antitumor activity. The safety and efficacy of Soto with PMab, a monoclonal antibody specific to EGFR, in KRAS p.G12C-mutated CRC are being evaluated in this ongoing phase Ib study (NCT04185883).

Methods

This study includes a dose exploration phase to identify a safe/tolerable daily oral dose of Soto with PMab (6mg/kg IV Q2W) in patients (pts) with previously treated mCRC, and a dose expansion phase. Dose exploration is reported.

Results

As of 4/23/21, 8 pts (5 female, median age: 60.5 yrs [range: 31-79]) were enrolled in dose exploration with 960 mg QD Soto and 6mg/kg IV Q2W PMab. Median number of lines of therapy for metastatic disease was 3.5 (range 1-10); 5 pts had prior Soto. Median treatment (tx) duration was 4.4 months (range: 1.4, 8.8). No dose limiting toxicities (DLTs) were observed during the DLT evaluation period (first 28 days). Tx-related adverse events (TRAEs) of any grade related to Soto or PMab were reported for 4 and 8 pts, respectively. No grade 4 or fatal TRAEs occurred. Two pts had PMab TRAEs leading to dose modification of PMab (1–dermatitis acneiform, 1–dry skin, rash, hypokalemia, hypomagnesemia) and 1 pt had a Soto TRAE leading to dose modification of Soto (diarrhea). There was 1 confirmed partial response, 5 stable disease (SD), 1 progressive disease (PD), and 1 not evaluated but with clinical PD. Of pts with prior Soto, 4 had decrease in sum of target lesions; 4 had SD and 1 with PD developed new lesions despite a decrease in size of target lesions. Sotorasib exposures were similar to those observed in monotherapy study.

Conclusions

Combination of Soto (960 mg QD) and PMab (6mg/kg IV Q2W) was safe and tolerable with promising efficacy in heavily pretreated pts with KRAS p.G12C-mutated CRC. AEs are consistent with known AEs for Soto and PMab. Updated safety and efficacy data will be presented.

Clinical trial identification

NCT04185883.

Editorial acknowledgement

Medical writing support was provided by Yang Li and Liz Leight (Amgen Inc.).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

M. Fakih: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Array BioPharma; Bayer; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis. G.S. Falchook: Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Advisory Role: Fujifilm; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Funding, Travel: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel: EMD Serono; Fujifilm; Millennium;: Sarah Cannon Research Institute; Financial Interests, Personal, Invited Speaker: Total Health Conferencing; Rocky Mountain Oncology Society; Financial Interests, Institutional, Funding, research funding: 3-V Biosciences; Abbisko; AbbVie; ADC Therapeutics; Aileron; American Society of Clinical Oncology; Amgen; ARMO; AstraZeneca; BeiGene; Bioatla; Biothera; Celldex; Celgene; Ciclomed; Curegenix; Curis; Cyteir; Daiichi; DelMar; eFFECTOR; Eli Lilly; EMD Serono; Epizyme; Exelixis; Fujifilm; Genmab; GlaxoSmithKline; Hutchison MediPharma; Ignyta; Incyte; Jacobio; Jounce; Kolltan; Loxo; MedImmune; Millennium; Merck; miRNA Therapeutics; National Institutes of Health; Novartis; OncoMed; Oncorus; Oncothyreon; Poseida; Precision Oncology; Prelude; Regeneron; Rgenix; Ribon; Strategia; Syndax; Taiho; Takeda; Tarveda; Tesaro; Tocagen; Turning Point Therapeutics; U.T. MD Anderson Cancer Center; Vegenics; Xencor. D.S. Hong: Financial Interests, Institutional, Research Grant: Bayer; Lilly; Genentech; LOXO; Pfizer; Amgen; Mirati; Ignyta; Merck; Daiichi Sankyo; Eisai; Adaptimmune; AbbVie; Astra-Zeneca; BMS; Genmab; Infinity; Kite; Kyowa; Medimmune; Molecular Template; Novartis; Takeda; Financial Interests, Personal, Other: Mirna; LOXO; Bayer; Baxter; Guidepoint Global; Oncoresponse; Janssen; Molecular Match. R.D. Yaeger: Financial Interests, Personal, Advisory Role: Array BioPharma/Pfizer; Natera; Mirati Therapeutics; Financial Interests, Institutional, Funding, research funding: Pfizer; Boehringer Ingelheim. E. Chan: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. O. Mather: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. P. Cardona: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. T. Dai: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. J. Strickler: Financial Interests, Personal, Advisory Board: Amgen; AstraZeneca; Bayer; Natera; Pfizer; SeaGen; Viatris; Financial Interests, Personal, Other, Consulting: Mereo; Non-Financial Interests, Institutional, Other, Coordinating PI: Amgen; Exelixis; Non-Financial Interests, Institutional, Principal Investigator, local PI: AbbVie; AStar D3; AstraZeneca; Curegenix; Daiichi Sankyo; Leap Therapeutics; Nektar; Roche Genentech; Sanofi; SeaGen.

Background

Leukemia is the tenth most common cause of cancer related deaths. In 2018, there were a total of 437,000 estimated new cases and 309,000 deaths of leukemia worldwide. The objective of this study is to observe the trends in mortality, incidence and disability-adjusted life years (DALYs) from all types of leukemia between 1990-2019 in European Union (EU) 15+ nations.

Methods

We extracted the data from the Global Burden of Disease Study database based on the International Classification of Diseases versions 10 and 9. Age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and DALYs were extracted for individual EU15+ countries per sex for each of the years 1990-2019, inclusive, and mortality-to-incidence indices (MII) were computed. All indices were reported per 100,000 population.

Results

ASIRs increased in 17/19 countries for males and 14/19 countries for females. The largest increase was in Germany (+56.4%) for males, and in Austria for females (+48.8%). All countries observed decreasing ASMRs for females and males except for males in the Netherlands (+1.9%). The greatest decreases were seen in Denmark for both males (-37.4%) and females (-38.9%). For both sexes, the MIRs decreased in all countries. The largest reductions were found in Ireland for males (-51.1%) and females (-54.7%). DALYs were decreased in all the countries for both genders. Denmark had the highest decreases for both males (-49.3%) and females (-50.1%). In 2019, Germany had the highest ASIR for males (26.7) and females (17.7). USA had the highest MIR for both males (0.57) and females (0.56). Greece showed the highest ASMR for males (8.2) and females (5.2) as well as DALY for males (205.1) and females (136.6).

Conclusions

Although incidence of leukemia is increasing in the majority of EU15+ countries, mortality, MIR as well as DALYs have shown a downwards trend. Possible explanations for the increases in incidence could relate to ageing populations, changes in leukemia diagnosis criteria (lowering the blast count for acute myeloblastic leukemia) in 2001, and increases in chemoradiation-related leukemias. ASMRs, MIRs and DALYs have consistently decreased possibly reflecting effective new treatments modalities especially for chronic lymphocytic leukemia.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Hepatocellular carcinoma is the third leading cause of cancer mortality worldwide. Globally the incidence is increasing with an estimated 900,000 new cases diagnosed in 2020. This study considers the geographical trends in disease burden from hepatocellular carcinoma. Data from 1990 to 2019 is explored to further understand the pattern of disease across EU15+ nations.

Methods

Observational study of The Global Burden of Disease database. Data were for age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for the years 1990-2019. Mortality to incidence ratios were computed MIR (MIR). Trends were analysed over time and sex-specific absolute and percentage change values were calculated for each country between the start (1991-1993) and the end (2017-2019) of the observation period.

Results

ASIRs increased in 17/19 countries in females and 18/19 countries in males. The greatest increases in ASIR were in Ireland (+149.9%) for females and Portugal (+178.8%) for males. ASMRs increased in all countries except Italy (for both sexes) and Sweden (for females). The largest rises in ASMR were in Australia (+134.8%) for females and Portugal (+159.1%) for males. MIR decreased in all countries except Denmark in males (+8.0) and females (+1.2). Ireland saw the greatest decline in MIR among females (-15.0%) and the United Kingdom for males (-16.4%). DALYs increased in all countries except Italy for both males and females, and Sweden for females.

Conclusions

The incidence of and mortality from hepatocellular carcinoma are increasing in the majority of EU15+ countries. The rise in mortality and fall in MIR suggests that outcomes from hepatocellular carcinoma are improving, despite an increased burden of disease.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.