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PURPOSE Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974 ). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor–positive, 25.2% (n = 131) human epidermal growth factor receptor 2–positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19–specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

Introduction: A significant proportion of patients with cancer who recover from Coronavirus Disease 2019 (COVID-19) may experience COVID-19 sequelae in the early post-infection phase, which negatively affect their continuity of care and oncological outcome. The long-term prevalence and clinical impact of the post-COVID-19 syndrome in patients with cancer are largely unknown. Methods: In this study, we describe the time course of COVID-19 sequelae in patients with non-advanced cancers enrolled in the OnCovid registry. Results: Overall, 186 patients were included, with a median observation period of 9.9 months (95%CI:8,8–11.3) post-COVID-19 resolution. After a median interval of 2.3 months post-COVID-19 (interquartile range: 1.4–3.7), 31 patients (16.6%) reported ≥1 sequelae, including respiratory complications (14, 7.6%), fatigue (13, 7.1%), neuro-cognitive sequelae (7, 3.8%). The vast majority of the patients were not vaccinated prior to COVID-19. COVID-19-related sequelae persisted in 9.8% and 8% of patients 6 and 12 months after COVID-19 resolution. Persistence of sequelae at first oncological follow-up was associated with history of complicated COVID-19 (45.2% vs 24.8%, p = 0.0223), irrespective of oncological features at COVID-19 diagnosis. Conclusion: This study confirms for the first time that, in a largely unvaccinated population, post-COVID-19 syndrome can affect a significant proportion of patients with non-advanced cancer who recovered from the acute illness. COVID-19 sequelae may persist up to 12 months in some patients, highlighting the need for dedicated prevention and supportive strategies.

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p

Oncology; Public health; COVID-19 Oncología; Salud pública; COVID-19 Oncologia; Salut pública; COVID-19 Background Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and severity of SARS-CoV-2 reinfections are unknown. Methods We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid (NCT04393974), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy diagnosed with COVID-19. Results As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40–620) from the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27–196). Most of the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11 patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The 14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients. Conclusion This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients, highlighting the importance of universal vaccination of patients with cancer. OnCovid is sponsored by Imperial College London and received direct project funding and infrastructural support by the NIHR Imperial Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Neither sponsor nor the funders of the study had any role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had access to all the data reported in the study.

Simple Summary Since the irruption of PARPi in the therapeutic armamentarium for ovarian cancer, concerns regarding post-progression treatment outcomes have emerged, owing to known crossed-resistance mechanisms between PARPi and platinum. In this multicentric retrospective series of ovarian cancer patients, we evaluated chemotherapy results upon progression to maintenance with PARPi in the relapsed setting. We further selected the population of platinum-sensitive patients (according to the classical definition) retreated with platinum (n = 74). In this platinum-sensitive population, overall response rate and survival outcomes of platinum rechallenge after PARPi were similar to historical series of the prePARPi era. However, within this group, analysis according to BRCA status showed that BRCA mutant patients (n = 35) presented higher rates of progression and worse survival outcomes under subsequent platinum than BRCA wild type patients (n = 39), with statistically significant differences. This is the largest real-world data series of ovarian cancer patients treated with platinum rechallenge in the post-PARPi scenario. Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8-17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6-9.2), and median OS (mOS) of 20.6 months (95% CI 13.6-28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2-22.2] and 10.3 [IQR 7.4-14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5-8.6) versus 7.5 months (95% CI 6.5-10.1, p = 0.03), and 16.4 (95% CI 9.3-27.5) versus 24.2 months (95% CI 17.2-NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by a rapid progression and a high resistance to treatments. Unlike other solid tumors, there has been a scarce improvement in emerging treatments and survival during the last years. A better understanding of SCLC biology has allowed for the establishment of a molecular classification based on four transcription factors, and certain therapeutic vulnerabilities have been proposed. The universal inactivation of TP53 and RB1, along with the absence of mutations in known targetable oncogenes, has hampered the development of targeted therapies. On the other hand, the immunosuppressive microenvironment makes the success of immune checkpoint inhibitors (ICIs), which have achieved a modest improvement in overall survival in patients with extensive disease, difficult. Currently, atezolizumab or durvalumab, in combination with platinum–etoposide chemotherapy, is the standard of care in first-line setting. However, the magnitude of the benefit is scarce and no predictive biomarkers of response have yet been established. In this review, we describe SCLC biology and molecular classification, examine the SCLC tumor microenvironment and the challenges of predictive biomarkers of response to new treatments, and, finally, assess clinical and molecular characteristics of long-term survivor patients in order to identify possible prognostic factors and treatment vulnerabilities.

Alternative dosage regimens for some anticancer therapies have been proposed in the midst of the SARS-COV-2 pandemic in order to protect the patients from attending to health care facilities. Flat-dosing of several immune-checkpoint inhibitors (ICIs), including nivolumab, have been established. Although generally well tolerated with no new safety signals, new dosages can associate novel individual toxicities. As the use of ICIs is increasing in cancer patients, the present case report is a reminder for clinicians of potential novel toxicities, as well as the need for an interdisciplinary approach for their recognition and treatment. We report the occurrence of a severe neurologic toxicity in a patient with non-small cell lung cancer (NSCLC) who developed should be changed to which occurred after two doses of extended higher interval flat-dose nivolumab despite two years of clinical stability on prior nivolumab regimen. Patient developed fever, language impairment and altered mental status. The work-up tests excluded other potential causes and the most likely diagnosis was meningoencephalitis. Fortunately, with medical treatment, which consisted of high dose steroids, the patient recovered to his baseline situation and symptoms did not recurred, even though nivolumab was resumed. Alternate ICI regimens may have unique immune-related adverse event profiles.

Introduction: CXC chemokines are a family of small, secreted, chemotactic molecules acting through the binding to their corresponding CXC receptors (CXCRs) and stimulating the migration of cells, most notably those of the immune system. They have been associated with both pro-tumor and anti-tumor activity. Previously, we reported increased expression and secretion levels of CXCL1, 2 and 8 in oxaliplatin (OXA)-resistant colorectal cancer (CRC) cell lines. The aim of this study is to evaluate the usefulness of measuring the serum levels of a CXC chemokine panel in CRC patients as prognostic and/or predictive biomarkers of first-line treatment. Material and Methods: In this multicenter study sera from advanced CRC patients to be treated with OXA-based schedules were collected at three different time points between November 2016 and June 2021: before treatment (PRET), at first response evaluation (EVAR) and at the time of progression/end of study (PROG). Levels of CXCL1, 2, 5, 6, 8, 9, 10, 11, 12, 13, 16 chemokines were analyzed using a custom Bio-plex Pro Human assay (Bio-Rad, USA) in a Luminex® 200 equipment. Comparisons of chemokines’ levels between Responders (R) and Non-Responders (NR) at different time-points were carried out using the Mann Whitney U and Wilcoxon tests. Log Rank and Cox regression were used to study differences in progression-free (PFS) and overall survival (OS); Chi-square or Fisher’s tests were used to study associations between categorical variables. All differences were considered statistically significant when p values ≤ 0.05. Results: A total of 107 patients were enrolled in this study: 72% male; median age 66 years old; metastasis: 78% liver, 41% lung; mutations: 44% KRAS, 4% BRAF; treatments: FOLFOX/XELOX = 30%/4% plus Bevacizumab/anti-EGFR = 36%/24%; 64% responders (complete response + partial response); 13% stable disease; 11% progressors. All chemokines could be detected in the samples. Levels below median (LBM) of CXCL1, 8, 11 and 13 correlated with better OS (HR=0.55 p=0.02; HR=0.47 p=0.005; HR=0.6 p=0.05; HR=0.54 p=0.02, respectively). LBM of CXCL16 correlated with better OS and PFS (HR=0.6 p=0.04; HR=0.6 p=0.005) and of CXCL5 with better PFS (HR 0.6 p 0.011); mean CXCL9 levels were lower in responders’ PRET samples (p=0.03) and LBM correlated with better OS (HR=0.5 p=0.019). In responders, all chemokines except CXCL10, 13 and 16 presented decreased levels at EVAR vs. PRET. Moreover, CXCL1, 2, 5, 8, 11 and 16 levels increased at PROG vs. EVAR. In non-responders, non-conclusive results were found. Conclusion: our results show that serum levels of specific CXC chemokines may be used as prognostic/predictive markers in metastatic CRC. Further analysis will be performed, and an update of this study will be presented in the AACR meeting. Citation Format: Sara Cabrero-de las Heras, Ferran Losa, Xavier Hernández-Yagüe, Gemma Soler, Cristina Bugés, Iosune Baraibar, Andrea Plaja, Eduard Teixidor, Eva Martínez-Balibrea. Luminex-based analysis of serum CXC chemokines showing their usefulness as prognostic and/or predictive biomarkers in metastatic colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3489.

Introduction/Background PARP inhibitors (PARPi) maintenance after Platinum (Pt) based chemotherapy (CT) significantly improves progression-free survival (PARPi-PFS) and PFS after subsequent (ssq) CT (PARPi-PFS2) in relapsed high grade serous ovarian cancer (HGSOC). Data regarding ssq CT is scarce, and PARPi/Pt crossed mechanisms of resistance may impact on outcome of ssq Pt. We provide Real-world-data on this issue. Methodology We included HGSOC p treated with ssq CT after progression to maintenance PARPi until 15th Jul 2020 in 3hospitals. Endpoints were related to this ssq CT: objective response rate (ORR), median(m) progression-free survival (PFS) and overall survival (OS). Multivariate Cox and logistic regression models were adjusted by BRCA status and Pt-free interval (PFI) (6–12 months(mo) vs ≥12 mo). Adjusted hazard ratios (aHR) and odds ratios (aOR) of the risk of progression/death and ORR, respectively, were reported with 95% confidence intervals (CI). Results 56p were identified (32p BRCAmut; 1p BRIP1mut). 4p (7.1%) received PARPi after 1st line CT, 26 (46.4%) after 2nd line and 26 (46.4%) after ≥3rd line. 34p (60.7%) received olaparib and 22 (39.3%) niraparib. m-PARPi-PFS in the recurrent setting was 7.5 mo (longer in BRCAmut: 10.1 vs 5.5 mo, p 0.03). m-PARPi-PFS2 was 15.8 mo (longer in BRCAmut: 20.9 vs 15.4 mo, p 0.07). Endpoints regarding ssq CT are shown in table1. ORR to ssq Pt was 33.3% and progression disease without any response 28.6%. ORR in p who received ssq Pt-free CT, ssq Pt with PFI 6–12 mo, and ssq Pt with PFI≥12 mo were 33.3%, 23.8% and 42.8%, respectively. Five complete responses occurred among BRCAmut p that had received PARPi in the recurrent setting. mPFS and mOS were significantly longer in the PFI≥12 subgroup vs the others (figure1). Focusing in p receiving ssq Pt, when adjusting by BRCA status: aOR of ORR in p with PFI≥12 vs 6–12 mo was 0.56 (95% CI: 0.13 – 2.30), aHR of mPFS between these two subgroups was 0.61 (95% CI: 0.30–1.20; p 0.16), and aHR of mOS was 0.20 (95% CI: 0.7–0.61, p 0.005). Results did not change when excluding the 4p who received PARPi as 1st line. Conclusion A trend towards higher benefit from ssq Pt after PARPi was observed in the PFI≥12 subgroup. Benefit from ssq Pt after PARPi in the PFI 6–12 subgroup was similar to benefit from CT in the non-Pt subgroup. The role of ssq Pt after PARPi in the PFI 6–12 subgroup warrants further research. Disclosures Andrea Plaja: travel grant for attending scientific meeting (Roche, Angelini). Marta Gil-Marin: speaking (Roche, Astra Zeneca, Pharmamar) and travel grants (Roche, Pharmamar, MSD). Beatriz Pardo: speaking (Roche, Astra Zeneca, MSD) and travel grants (Roche, MSD, GSK). Josep Maria Piulats: advisory board (Astra Zeneca, MSD, Clovis, BeiGene) and travel grants (Astra Zeneca, MSD, BeiGene). Maria Pilar Barretina: advisory board (Roche, Astra Zeneca, GSK, Clovis Oncology), speaking (Roche, Astra Zeneca, GSK, Clovis Oncology, Pharmamar) and travel grants (Roche, GSK, Astra Zenaca, Pharmamar). Claudia Fina: travel grants (Roche, MSD, Pfizer, Bristol-Myers) Margarita Romeo: advisory boards (AZ, TESARO) and travel grants (Pfizer). Iris Teruel, Anna Esteve and Andrea Gonzalez have nothing to disclosure.

Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the recommended treatment, with the highest level of evidence, for patients with muscle-invasive bladder cancer (MIBC). However, only a minority of patients receive this treatment, mainly due to patient comorbidities, the relatively small survival benefit, and the lack of predictive biomarkers to select those patients most likely to benefit from this multimodal approach. In addition, adjuvant chemotherapy has been recommended for patients with high-risk MIBC, although randomized trials have not provided conclusive evidence on the impact of this approach. At present, however, this situation is changing, largely due to our improved knowledge of the molecular biology of bladder cancer, which has enabled us to identify new prognostic and predictive biomarkers that can be used to select the most appropriate treatment for each patient. Moreover, new active treatments, especially immunotherapy, have shown promising results in the neoadjuvant setting. In addition, the gene expression profile of bladder tumors can be used to classify them into different subtypes, which correlate with specific clinical-pathological characteristics and with treatment response or resistance. Therefore, the main objective for the near future is to introduce these translational breakthroughs into routine clinical practice in order to personalize treatment for each patient.

Mechanical heart valves (MHV) require life-long anticoagulation with vitamin K antagonists (VKA), but anticoagulation management is complex in patients with cancer due to a high risk of thrombosis and bleeding. This is a retrospective, single-center study to assess anticoagulation management and thrombotic (stroke/valve thrombosis) and bleeding events in patients with active cancer and MHV. The incidence of thrombotic complications was compared to a control group (matched 1:1) of patients with MHV but without cancer. We included 48 patients, 60% of whom had aortic prostheses, 23% mitral prostheses and 17% both types. All patients received VKA as anticoagulant. With a median follow-up of 5.12 years, we observed two arterial thrombotic events (two strokes and no heart valve thrombosis). The 5-year incidence (95% confidence interval [CI]) of stroke/valve thrombosis was 5.7% (0.9-17.9%). The control group had a similar incidence of stroke/valve thrombosis (5-year incidence 7.9% [95%CI 2-19.8], p = 0.16). There were also 15 major bleeding episodes in the cancer group, 11 of which were related to a surgical procedure. The 5-year incidence (95% CI) of major bleeding was 32.9% (18.5-48%), and that of major bleeding unrelated to any procedure was 10.3% (3-23%). We found a low incidence of thrombotic events in this series of patients with active cancer and MHV who were anticoagulated with VKA. However, the incidence of bleeding was high, particularly in relation to invasive procedures.