Preliminary analysis of an expanded access study of the fixed-dose combination of pertuzumab (P) and trastuzumab (H) for subcutaneous injection (PH FDC SC) for athome administration (admin) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) during the COVID-19 pandemic

Background: Standard of care for HER2+ early/first-line metastatic BC (EBC/MBC) is P + H and concurrent chemotherapy (CT);PH FDC SC offers faster, more convenient admin vs intravenous (IV) P + H. COVID-19 has caused unprecedented strain on healthcare systems and disruption to cancer care;treatment (Tx) at home may: enable pts to continue cancer Tx;reduce exposure to COVID-19;free up hospital resources. This study's main objectives: to enable continuity of care during COVID-19;to assess safety of PH FDC SC given at home. Methods: This is an ongoing single-arm, hybrid, decentralized clinical trial (NCT04395508). Pts with HER2+ EBC/MBC who completed concurrent CT with P + H IV and are receiving/about to receive maintenance P + H IV, PH FDC SC, or H SC are switched to PH FDC SC given at home by a home health nursing provider (HHNP) until disease progression, unacceptable toxicity, pt withdrawal, or physician recommendation (pts with EBC will complete ≤18 cycles). The study endpoint is safety. A subset of pts took part in HARRIET, a substudy of at-home cardiac surveillance with artificial intelligence-guided cardiac ultrasound and optional 6L ECG acquired by an HHNP. Results: Data for 114 pts (1 male) were available at cutoff (Jan 19, 2022): 18 (16%) completed Tx;20 (18%) discontinued;76 (67%) remain on study;79 (69%) had a COVID-19 vaccine while on study. Median age was 49 years;pts were balanced between EBC (n = 55, 48%) and MBC (n = 59, 52%);received a median of 6 (EBC) and 8 (MBC) cycles;and were from metropolitan (n = 109), urban (n = 4), and rural (n = 1) areas. 11 pts tested COVID-19-positive during the Tx phase: 8 continued Tx after appropriate COVID-19 Tx and/or quarantine. Safety is summarized in the table. No new adverse events (AEs) emerged due to home admin. AEs of special interest were grade (gr) 1-2: admin-related reactions (n = 76, 67%), hypersensitivity (n = 5, 4%), cardiac dysfunction (n = 4, 4%), except 1 case of gr ≥3 diarrhea. AEs leading to study Tx discontinuation or interruption/dose reduction occurred in 3 (3%) and 15 (13%) pts. A subset of 7 pts completed at-home cardiac surveillance testing;quantitative assessment of left ventricular ejection fraction was feasible in 3 (43%);5 (71%) preferred at-home surveillance to clinic. Conclusions: In this preliminary analysis, safety of PH FDC SC at home was consistent with the established P + H safety profile, indicating that PH FDC SC at home is a viable option for continuing BC care during and beyond COVID-19.

COVID-19 positivity rates in patients with an active cancer diagnosis in the University of California Cancer Consortium

Background: The impact of active cancer on susceptibility to coronavirus disease 2019 (COVID-19) remains controversial. This study leverages the infrastructure across the University of California (UC) Cancer Consortium, pooling electronic health record (EHR) data to assess the relationship between active cancer diagnoses (n=151,392) and COVID-19 positivity. Methods: In this cohort study, patients with COVID-19 test results and active cancer diagnoses were identified from the UC Health System COVID Research Data Set (CORDS). This data set collects COVID-19 test results from the 5 academic medical centers in the UC Health System and their NCI-designated Comprehensive Cancer Centers. COVID-19 test results were identified by Logical Observation Identifiers Names and Codes (LOINC). Active cancer was defined as an EHR-based malignant diagnosis within 9 months of testing, irrespective of active therapy. Total daily positivity rates were aggregated, and overall rates were compared across patients with and without active cancer using the Pearson’s Chi-squared test. Results: We identified 1,032,588 COVID-19 tests from March 3, 2020 to April 15, 2021, with 151,392 tests (14.7%) associated with an active cancer diagnosis. Monthly trends in positivity rates throughout the pandemic were similar between patients with and without cancer (Table). Overall positivity was lower in patients with active cancer (2.0% versus 4.4%;p<0.001). This was consistent across individual UC sites. [Formula presented] Conclusions: COVID-19 positivity rates were not increased for individuals with active cancer diagnoses in the UC Cancer Consortium. A lower positivity rate amongst cancer patients may be due to demographic, behavioral, occupational or environmental factors, as well as greater asymptomatic testing of cancer patients at some UC sites. Interactions with local prevalence and patient and cancer characteristics will be presented. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Expected medium and long term impact of the COVID-19 outbreak in oncology

Background: The ongoing SARS-CoV-2 pandemic and ensuing coronavirus disease (COVID-19) is challenging cancer care and services worldwide. Methods: A 95 items survey was distributed worldwide by 20 oncologists from 10 of the most affected countries in order to evaluate the impact on organization of oncological care. Results: 109 representatives from oncology centers in 18 countries (62.4% academic hospitals) filled out the survey (June 17 – July 14, 2020). A swab or gargle test is systematically performed before day care unit or overnight stay admissions in 27.5% and 58.7% of the centers, respectively. A local registry (64.2%) and systematic tracing (77.1%) of infected patients was organized in many centers. Treatment modalities mostly affected by the pandemic (cancellation/delay) were surgery (44.1%) and chemotherapy (25.7%). Earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2 % of participants agree that under-treatment is a major concern. At the pandemic peak, teleconsultations were performed for follow-up (94.5%), for oral therapy (92.7%), but also for patients receiving immunotherapy (57.8%) or chemotherapy (55%). Approximately 82% of participants estimate that they will continue to use telemedicine. Most participants reported more frequent use of virtual tumor boards (82%) and oncological team meetings (92%), but 45% disagree that virtual meetings are an acceptable alternative to live international meetings. Although 60.9% report reduced clinical activity during the pandemic peak, only 28.4% had an increased scientific activity. Only 18% of participants estimate that their well-being will not recover to previous levels by the end of the year;63% indicate easily accessible psychological support for caregivers, but only 10% used or planned to use it. All clinical trial activities are or will soon be reactivated in 72.5% of the centers. Major study protocol violations/deviations were observed in 27.5% and significant reductions of clinical trial activities are expected by 37% of centers this year. Conclusions: COVID-19 has a major impact on organization of patient care, well-being of caregivers, continued medical education and clinical trial activities in oncology. Legal entity responsible for the study: The authors. Funding: Fondation Léon Fredericq. Disclosure: G. Jerusalem: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly;Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen;Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca;Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo;Advisory/Consultancy: AbbVie;Travel/Accommodation/Expenses: MedImmune;Travel/Accommodation/Expenses: Merck KGaA. G. Curigliano: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics;Speaker Bureau/Expert testimony, Writing engagement: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony: Foundation Medicine;Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony: Celltrion;Leadership role, Scientific Affairs Group: Ellipsis;Speaker Bureau/Expert testimony, Writing engagement: BMS;Speaker Bureau/Expert testimony: MSD;Advisory/Consultancy: Mylan. M. Campone: Honoraria (self), Advisory/Consultancy: GT1;Honoraria (institution), Advisory/Consultancy: Sanofi;Honoraria (institution), Advisory/Consultancy: Pierre-Favre;Honoraria (institution), Advisory/Consultancy: AstraZeneca;Honoraria (institution), Advisory/Consultancy: Servi r;Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Honoraria (institution), Advisory/Consultancy: AbbVie;Honoraria (institution), Advisory/Consultancy: Accord;Honoraria (institution), Advisory/Consultancy: Pfizer;Speaker Bureau/Expert testimony: Lilly. M. Martin: Advisory/Consultancy, Research grant/Funding (institution): Roche;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy, Research grant/Funding (institution): Puma;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Amgen;Advisory/Consultancy: Taiho Oncology;Advisory/Consultancy: Daichii Sankyo;Advisory/Consultancy: PharmaMar;Advisory/Consultancy: Eli Lilly;Advisory/Consultancy: Pfizer. M. Cristofanilli: Advisory/Consultancy: CytoDyn;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer;Advisory/Consultancy: Lilly;Advisory/Consultancy: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Foundation Medicine;Advisory/Consultancy: G1 Therapeutics;Advisory/Consultancy: Sermionexx;Advisory/Consultancy: Genentch. L. Pusztai: Honoraria (self), Research grant/Funding (institution), Clinical trial support: Merck;Honoraria (self), Research grant/Funding (institution), Clinical trial support: AstraZeneca;Honoraria (self), Research grant/Funding (institution), Clinical trial support: Seattle Genetics;Honoraria (self): Novartis;Honoraria (self), Research grant/Funding (institution), Clinical trial support: Roche Genentech;Honoraria (self): Eisai;Honoraria (self): Daiichi;Honoraria (self): Syndax;Honoraria (self): Immunomedics. R. Bartsch: Advisory/Consultancy: Accord;Honoraria (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (institution): Daiichi;Advisory/Consultancy, Travel/Accommodation/Expenses: Eli-Lilly;Advisory/Consultancy, Travel/Accommodation/Expenses: MSD;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy, Research grant/Funding (institution): Roche;Advisory/Consultancy: Puma;Advisory/Consultancy: Pierre-Favre;Advisory/Consultancy: Sandoz;Advisory/Consultancy: Eisai. M. Tagliamento: Travel/Accommodation/Expenses: Roche;Travel/Accommodation/Expenses: Bristol-Myers Squibb;Travel/Accommodation/Expenses: AstraZeneca;Travel/Accommodation/Expenses: Takeda;Travel/Accommodation/Expenses: Novartis;Travel/Accommodation/Expenses: Amgen. J. Cortés: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Celgene;Advisory/Consultancy: Cellestia;Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca;Advisory/Consultancy: Biothera Pharmaceutical;Advisory/Consultancy: Merus;Advisory/Consultancy: Seattle Genetics;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo;Advisory/Consultancy: Erytech;Advisory/Consultancy: Athenex + Polyphor;Advisory/Consultancy, Shareholder/Stockholder/Stock options: MedSIR;Honoraria (self), Advisory/Consultancy: Lilly;Advisory/Consultancy: Servier;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp Dome;Advisory/Consultancy: GSK;Advisory/Consultancy: Leuko;Advisory/Consultancy: Bioasis;Advisory/Consultancy: Clovis Oncology;Advisory/Consultancy: Boehringer Ingelheim;Honoraria (self), Travel/Accommodation/Expenses: Novartis;Honoraria (self), Travel/Accommodation/Expenses: Eisai;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self): Samsung Bioepis;Research grant/Funding (institution): Ariad Pharmaceuticals;Research grant/Funding (institution): Baxalta GMBH/Servier Affaires;Research grant/Funding (institution): Bayer Healthcare;Research grant/Funding (institution): F. Hoffmann-La Roche;Research grant/Funding (institution): Guardanth Health;Research grant/Funding (institution): Piqur THerapeutics;Research grant/Funding (institution): Puma C;Research grant/ unding (institution): Queen Mary University of London. E.M. Ciruelos: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. H.S. Rugo: Research grant/Funding (institution): Eisai;Research grant/Funding (institution): Genentech;Research grant/Funding (institution): Lilly;Research grant/Funding (institution), Travel/Accommodation/Expenses: MacroGenics;Research grant/Funding (institution): Merck;Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Research grant/Funding (institution): Obi Pharma;Research grant/Funding (institution): Odonate Therapeutics;Research grant/Funding (institution): Immunomedics;Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo;Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Advisory/Consultancy: Samsung;Advisory/Consultancy: Celtrion;Travel/Accommodation/Expenses: Mylan;Travel/Accommodation/Expenses: AstraZeneca. All other authors have declared no conflicts of interest.

IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer

Background: Based on findings from IMpassion130, international guidelines now recommend atezolizumab (A) + nab-paclitaxel (nP) for patients (pts) with locally advanced or metastatic TNBC (mTNBC) whose tumours express PD-L1 on tumour-infiltrating immune cells (IC). Here we report prespecified final OS and long-term safety results. Methods: The study design and final PFS analysis have been reported (Schmid NEJM 2018). Pts were randomised 1:1 to A + nP or placebo (P) + nP. Co-primary endpoints were PFS (tested in parallel in ITT and PD-L1+ pts) and OS (tested hierarchically in ITT and, if significant, in PD-L1+ pts). Results: As of 14 April 2020, 666/902 pts (73.8%) had died;median OS follow-up was 18.8 mo (IQR, 8.9-34.7 mo). 6% of pts in the A + nP arm and 2% in the P + nP arm remained on any treatment. OS data are in the Table. 460 A + nP arm pts and 430 P + nP arm pts were safety evaluable, of whom 8% and 3%, respectively, received nP for up to 24 mo. Similarly, 5% in the A + nP arm received nP for ≥ 24 mo (vs 1% in the P + nP arm). Respectively, 51% vs 43% had a G 3-4 AE;≈ 1% per arm had a G 5 AE (no new G 5 AEs since last analysis;no patterns seen);24% vs 19% had a serious AE, and 59% vs 42% had an AE of special interest (G 3-4 in 8% vs 5%). No confirmed or suspected COVID-19 AEs were reported. 19% in the A + nP arm and 8% in the P + nP arm had an AE leading to treatment discontinuation (most commonly due to neuropathy);in 18% and 8%, respectively, AEs led to nP discontinuation, and in 8% and 1%, AEs led to A or P discontinuation. Conclusions: While OS differences for A + nP vs P + nP in the IMpassion130 ITT population were not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed in PD-L1+ pts (7.5-mo median OS improvement). A + nP remained safe and tolerable with longer follow-up. Results from this final and mature OS analysis are consistent with prior interim analyses. [Formula presented] Clinical trial identification: NCT02425891. Editorial acknowledgement: Medical writing assistance for this abstract was provided by Ashley J. Pratt, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd. Funding: F. Hoffmann-La Roche, Ltd. Disclosure: L.A. Emens: Honoraria (self): AbbVie, Amgen, Celgene, Chugai, Gritstone, MedImmune, Peregrine, Shionogi, Syndax;Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Bayer, MacroGenics, Replimune, Vaccinex;Travel/Accommodation/Expenses: Bristol Myers Squibb, Genentech/Roche, Novartis;Research grant/Funding (institution): Aduro Biotech, AstraZeneca, The Breast Cancer Research Foundation, Bristol Myers Squibb, Bolt Therapeutics, Corvus, The US Department of Defense, EMD Serono, Genentech, Maxcyte, Merck, The National Cancer Institute, The NSABP Foundation, Roche, The Transl;Licensing/Royalties: Aduro;Advisory/Consultancy: Roche. S. Adams: Research grant/Funding (institution): Genentech;Research grant/Funding (institution): Merck, Amgen, BMS, Novartis, Celgene, Daiichi Sankyo. C.H. Barrios: Advisory/Consultancy: Boehringer- Ingelheim;Advisory/Consultancy: GSK;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy, Research grant/Funding (institution): Pfizer;Advisory/ Consultancy, Research grant/Funding (institution): Roche/Genentech;Advisory/Consultancy: Eisai;Advisory/Consultancy, Research grant/Funding (institution): Merck;Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca;Non-remunerated activity/ies: Bayer;Research grant/ Funding (institution): AbbVie;Research grant/Funding (institution): Amgen;Research grant/Funding (institution): Astellas;Research grant/Funding (institution): BMS;Research grant/Funding (institution): Celgene;Research grant/Funding (institution): Lilly;Research grant/Funding (institution): Medivation;Research grant/Funding (institution): Sanofi;Research grant/Funding (institution): Taiho Pharmaceutical;Research grant/Funding (institution) Mylan;Research grant/Funding (institution): Merrimack;Research grant/Funding (institution): Biomarin;Research grant/Funding (institution): Daiichi Sankyo;Research grant/Funding (institution): Abraxis BioScience;Research grant/Funding (institution): AB Science;Research grant/Funding (institution): Asana BioSciences;Research grant/Funding (institution): Exelixis, Research grant/Funding (institution): ImClone Systems, Research grant/Funding (institution): LEO Pharma;Research grant/Funding (institution): Millennium;Advisory/Consultancy: Merck Sharp and Dohme;Advisory/Consultancy: AstraZeneca. V.C. Dieras: Honoraria (self), Advisory/Consultancy: Roche/Genentech, Pfizer, Lilly, Novartis, Daiichi Sankyo, AstraZeneca, AbbVie, Seattle Genetics, Odonate, MSD. H. Iwata: Honoraria (self), Advisory/Consultancy: Chugai;Honoraria (self), Advisory/Consultancy: Novartis, AstraZeneca, Pfizer, Lilly, Daiichi-Sankyo, Eisai, Kyowa Kirin;Non-remunerated activity/ies: MSD, Bayer, BI, Nihon, Kayaku, Sanofi. S. Loi: Research grant/Funding (institution), Non-remunerated activity/ies: Novartis, BMS, Roche-Genentech, Merck;Research grant/Funding (institution): Puma, Eli Lilly, Pfizer;Unpaid consultant: Seattle Genetics;Unpaid consultant: Pfizer;Unpaid consultant: Novartis;Unpaid consultant: BMS;Unpaid consultant: AstraZeneca;Unpaid consultant: Roche/Genentech;Advisory/Consultancy (institution): Aduro Biotechnology. H.S. Rugo: Research grant/Funding (institution): Pfizer, Novartis, Lilly, Genentech/Roche, Merck, OBI, Eisai, Plexxikon, Immunomedics;Research grant/Funding (institution), Travel/Accommodation/Expenses: Macrogeneics, Daiichi;Travel/Accommodation/Expenses: Puma, Mylan, Genentech/Roche, Novartis, Pfizer;Honoraria (self): Celltrion. A. Schneeweiss: Research grant/Funding (institution): Celgene, Roche, AbbVie, Molecular Partner;Advisory/Consultancy: Roche AstraZeneca;Travel/Accommodation/Expenses: Celgene, Roche, Pfizer;Honoraria (self): Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly. E.P. Winer: Honoraria (self): Lilly, Genentech, Infinite MD, Carrick Therapeutics, GSK, Jounce, Genomic HEalth, Merck, Seattle Genetics;Honoraria (self), Leadership role: Leap. S. Patel: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. V. Henschel: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. A. Swat: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. M. Kaul: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. L. Molinero: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. S.Y. Chui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. P. Schmid: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant, spouse – consulting for Genentech: Roche;Honoraria (self): Medscape;Honoraria (self), Advisory/Consultancy: AstraZeneca;Honoraria (self): GI Therapeutics;Honoraria (self): Health Interactions;Advisory/Consultancy: Pfizer;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy: Merck;Advisory/Consultancy: Boehringer Ingelheim;Advisory/Consultancy: Bayer;Advisory/Consultancy: EISAI;Advisory/Consultancy: Celegence;Advisory/Consultancy: Puma;Research grant/Funding (institution), Spouse/Financial dependant, spouse – consulting for Genentech: Genentech;Research grant/Funding (institution): Oncogenex.