PIVOT-10: Phase II study of bempegaldesleukin plus nivolumab in cisplatin-ineligible advanced urothelial cancer

The choice of first-line therapy for patients with metastatic urothelial cancer (mUC) is based on cisplatin-eligibility and programmed death-ligand 1 (PD-L1) status. For patients with mUC who are ineligible for cisplatin and with low PD-L1 expression, chemotherapy-based regimens are the only approved first-line option. In a Phase I/II trial of the chemotherapy-free regimen, bempegaldesleukin (BEMPEG; NKTR-214) plus nivolumab, patients with locally advanced or mUC experienced tumor responses regardless of baseline PD-L1 expression (objective response rates: 50 and 45% in patients with PD-L1-positive and-negative tumors, respectively). The Phase II PIVOT-10 study (NCT03785925), evaluates efficacy and safety of first-line BEMPEG plus nivolumab in cisplatin-ineligible patients with locally advanced or mUC. Most patients will have low PD-L1 expression. Primary end point: objective response rates (including complete response). © 2020 Robert A Huddart and co-authors

Erratum to ‘Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial’

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Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research

Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes

Objectives: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). Patients and Methods: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). Results: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43–1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73–1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81–1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05–0.91 and aHR 1.66, 95% CI 1.06–2.59), respectively). Conclusion: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy. © 2021 The Authors BJU International © 2021 BJU International Published by John Wiley & Sons Lt

Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin

Background: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes. Patients and Methods: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors. Results: A total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings. Conclusion: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC. © 202

A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

BACKGROUND: While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1). OBJECTIVE: We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study. DESIGN, SETTING, AND PARTICIPANTS: Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated. RESULTS AND LIMITATIONS: Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation. CONCLUSIONS: We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued. PATIENT SUMMARY: With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE  HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival. Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved

metastatic, trastuzumab-naive breast cancer: real-life practice outcomes

PurposeIn this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients.MethodsThis study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers.ResultsMedian age was 51 (22-82). Median PFS was 28.5months, while median OS was 40.3months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8m vs. 28.5m; p=0.002) and OS (26.7m vs. 40.3m; p=0.009). Patients older than 65years of age (n: 42, 13.2%) had significantly lower OS results (19.8m vs. 40.3m; p=0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure.ConclusionsOur RLP trial included only visceral metastatic, trastuzumab-naive BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.C1 [Esin, Ece; Oksuzoglu, B.; Erdur, E.; Demirci, U.] Univ Hlth Sci, Dept Med Oncol, Dr AY Ankara Oncol Educ & Res Hosp, Ankara, Turkey.[Bilici, A.] Medipol Univ, Int Hlth Ctr, Dept Med Oncol, Istanbul, Turkey.[Cicin, I.; Kostek, O.] Trakya Univ, Dept Med Oncol, Edirne, Turkey.[Kaplan, M. A.] Dicle Univ, Dept Med Oncol, Fac Med, Diyarbakir, Turkey.[Aksoy, S.; Aktas, B. Y.] Hacettepe Univ, Dept Med Oncol, Fac Med, Ankara, Turkey.[Ozdemir, O.; Alacacioglu, A.] Izmir KC Univ, Ataturk Educ & Res Hosp, Dept Med Oncol, Izmir, Turkey.[Cabuk, D.] Kocaeli Univ, Fac Med, Dept Med Oncol, Izmit, Turkey.[Sumbul, A. T.] Baskent Univ, Dept Med Oncol, Adana Hosp, Adana, Turkey.[Sakin, A.] Istanbul Okmeydani Educ & Res Hosp, Dept Med Oncol, Istanbul, Turkey.[Paydas, S.; Yetisir, E.] Cukurova Univ, Dept Med Oncol, Fac Med, Adana, Turkey.[Er, O.; Basaran, G.] Acibadem MAA Univ, Acibadem Maslak Hosp, Dept Med Oncol, Istanbul, Turkey.[Korkmaz, T.; Oyan, B.] Acibadem MAA Univ, Acibadem Altunizade Hosp, Dept Med Oncol, Istanbul, Turkey.[Yildirim, N.] Dr Ersin Arslan Training & Res Hosp, Dept Med Oncol, Gaziantep, Turkey.[Sakalar, T.] Erciyes Univ, Dept Med Oncol, Fac Med, Kayseri, Turkey.[Demir, H.] Kayseri Educ & Res Hosp, Univ Hlth Sci, Dept Med Oncol, Kayseri, Turkey.[Artac, M.; Karaagac, M.] Necmettin Erbakan Univ, Meram Med Fac, Dept Med Oncol, Konya, Turkey.[Harputluoglu, H.; Bilen, E.] Inonu Univ, Dept Med Oncol, Turgut Ozal Med Ctr, Malatya, Turkey.[Degirmencioglu, S.] Pamukkale Univ, Dept Med Oncol, Fac Med, Denizli, Turkey.[Aliyev, A.] Bezmialem Univ, Dept Med Oncol, Fac Med, Istanbul, Turkey.[Cil, T.; Olgun, P.] Adana City Hosp, Univ Hlth Sci, Dept Med Oncol, Adana, Turkey.[Gumusay, O.] Gaziosmanpasa Univ, Dept Med Oncol, Fac Med, Tokat, Turkey.[Demir, A.] Univ Hlth Sci, Dept Med Oncol, Istanbul Okmeydani Educ & Res Hosp, Istanbul, Turkey.[Tanrikulu, E.; Yumuk, P. F.] Marmara Univ, Dept Med Oncol, Fac Med, Istanbul, Turkey.[Imamoglu, Inanc] Univ Hlth Sci, Ankara Diskapi Educ & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Cetin, B.] RTE Univ, Dept Med Oncol, Fac Med, Rize, Turkey.[Haksoyler, V.] Univ Hlth Sci, Diyarbakir GY Educ & Res Hosp, Dept Med Oncol, Diyarbakir, Turkey.[Karadurmus, N.; Erturk, I.] Univ Hlth Sci, Gulhane Educ & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Evrensel, T.; Yilmaz, H.] Uludag Univ, Dept Med Oncol, Fac Med, Bursa, Turkey.[Beypinar, I.] Afyon Kocatepe Univ, Dept Med Oncol, Fac Med, Afyon, Turkey.[Kocer, M.] Isparta SD Univ, Dept Med Oncol, Fac Med, Isparta, Turkey.[Pilanci, K. N.] Univ Hlth Sci, Dept Med Oncol, Haseki Educ & Res Hosp, Istanbul, Turkey.[Seker, M.; Urun, Y.] Ankara Bayindir Hosp, Dept Med Oncol, Ankara, Turkey.[Urun, Y.] Ankara Univ, Dept Med Oncol, Fac Med, Ankara, Turkey.[Yildirim, N.; Eren, T.] Univ Hlth Sci, Numune Educ & Res Hosp, Dept Med Oncol, Ankara, Turkey

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. NCT04354701