Characteristics of severe adverse events after peptide vaccination for advanced cancer patients: Analysis of 500 cases

Abstract Background Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. Methods To examine the potential confounding impact of such variables, we analyzed advanced cancer patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI. We tested the associations between developing ST, stratified as no (n = 617), mild (n = 191), and severe (n = 63), and progression-free survival (PFS) and overall survival (OS) in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival associating with adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Results Both mild and severe ST were significantly associated with improved PFS and OS (all P < 0.001). However, when adjusting for the time from treatment initiation to time of skin event, severe ST was not associated with PFS benefit both in univariable and multivariable analyses (P = 0.729 and P = 0.711, respectively). Receiving systemic steroids for ST did not lead to significant differences in PFS or OS compared to patients who did not receive systemic steroids. Conclusions Our data reveal the influence of time to event and its severity as covariates in analyzing the relationship between ST and ICI outcomes. These differences in outcomes cannot be solely explained by the use of immunosuppressive medications, and thus highlight the importance of host- and disease-intrinsic factors in determining ICI response and toxicity. Trial registration: The patient data used in this manuscript come from patients who were prospectively enrolled in two institutional review board-approved databases at NYU Langone Health (institutional review board #10362 and #S16-00122).

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Digitally captured step counts for evaluating performance status in advanced cancer patients: A single cohort, prospective trial (Digi-STEPS).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps6651 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS6651-TPS6651

Author(s):

Gillian Gresham ◽

Andrew Eugene Hendifar ◽

Jun Gong ◽

Arash Asher ◽

Christine S. Walsh ◽

...

Keyword(s):

Adverse Events ◽

Cancer Patients ◽

Advanced Cancer ◽

Performance Status ◽

Advanced Cancer Patients ◽

Step Counts ◽

Wide Range ◽

Ecog Ps ◽

Single Cohort

TPS6651 Background: Advanced cancer patients undergo dynamic changes in their functionality and physical activity over the course of their treatment. Monitoring patient function is important because it can inform treatment decisions and allow for timely and appropriate intervention. Current scales that assess patient function, such as the ECOG Performance Status (PS), are limited in their ability to capture the wide range in activity that cancer patients can experience on a daily basis outside of the clinic setting. Given recent technological advances in wearable activity monitors, we can collect real-time, objective information about a patient’s daily activity including steps, stairs, heart rate, sleep, and activity intensity. Thus, the primary objective of this study is to determine whether longitudinal changes in objectively-assessed activity are associated with change in physician-rated ECOG PS. Methods: This is a prospective, single cohort trial being conducted at Cedars-Sinai Medical Center. Stage 3/4 cancer patients who are English or Spanish-speaking, ambulatory (assistive walking devices are allowed) and expected to be seen for treatment or follow-up with their oncologist at least every 8 weeks are eligible for study. Consenting patients will be asked to wear a Fitbit Charge HR continuously for 8 weeks during the study period and for one week prior to the 6 month and 1 year follow-up visits. Primary outcomes are change in average daily step counts and ECOG PS at 8 weeks from baseline. Secondary outcomes include: 1) Change in NIH PROMIS patient-reported outcomes (physical function, pain, sleep, emotional distress, and fatigue), 2) Change in frailty status at 8 weeks, 3) Occurrence of adverse events, and 4) 6-month and 1-year survival outcomes. Baseline assessments include a physical exam, medical history, and frailty assessment. The attending oncologist will rate the patient's ECOG PS at baseline and at the end-of-study visit. Weekly NIH PROMIS questionnaires will be administered online over the 8-week study and again at 6 months and 1 year follow-up. The occurrence of serious cancer-related adverse events, chemotherapy-associated toxicities, and hospitalizations will be documented up to 12 weeks from baseline. Survival will be assessed at 6 months and 1 year. Accrual is ongoing with 20 patients currently enrolled of a target sample size of 60 patients. Clinical trial information: NCT03757182.

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A systematic review on the emerging association between the occurrence of immune-related adverse events and clinical outcomes with checkpoint inhibitors in advanced cancer patients

Seminars in Oncology ◽

10.1053/j.seminoncol.2019.10.003 ◽

2019 ◽

Vol 46 (4-5) ◽

pp. 362-371 ◽

Cited By ~ 10

Author(s):

Alessio Cortellini ◽

Sebastiano Buti ◽

Veronica Agostinelli ◽

Melissa Bersanelli

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Cancer Patients ◽

Clinical Outcomes ◽

Advanced Cancer ◽

Checkpoint Inhibitors ◽

Advanced Cancer Patients

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Transfusion Practices In Advanced Cancer Patients

10.21203/rs.3.rs-172971/v1 ◽

2021 ◽

Author(s):

Sara Marote ◽

Joana Marinho ◽

Maria Cândida Silva ◽

José António Ferraz Gonçalves

Keyword(s):

Adverse Events ◽

Cancer Patients ◽

Advanced Cancer ◽

Care Service ◽

Palliative Care Service ◽

Advanced Cancer Patients ◽

Functional Changes ◽

Ecog Ps ◽

Rbc Transfusion ◽

Symptomatic Benefit

Abstract Purpose: Anemia is highly prevalent in patients with advanced cancer and adversely affects quality of life. There is limited data on the frequency, clinical utility and effectiveness of red blood cell transfusions (RBC), and no randomized controlled trials or clinical practice guidelines are available. The aim of this study was to evaluate clinician practices on RBC transfusion in an oncologic palliative care service (PCS) and its impact in patients’ symptoms, adverse events and overall survival.Methods: Retrospective analyses of all advanced cancer patients who received RBC transfusions admitted, during a 3-year period. Pre-blood counts, reason for transfusion, subjective benefit and objective outcomes were listed.Results: We identified 179 patients with a mean age of 67 years. A total of 435 RBC units, during 301 transfusion episodes were recorded. Asthenia/fatigue was the most frequent symptom (68%). The mean pretransfusion hemoglobin (Hb) was 6.85 g/dL and 48% patients had an Hb above 7 g/dL. Symptomatic benefit was achieved in 36% of patients. Adverse events were reported in 4%, with a 30-day survival rate of 57%. A statistically significant association between ECOG performance status (ECOG-PS) and symptomatic benefit was found (p=0.005). Hemoglobin level pre-transfusion, ECOG-PS and symptomatic benefit with transfusions were significantly associated with survival.Conclusion: This study suggests that advanced cancer patients with a higher level of functioning may have a bigger benefit from RBC transfusion. Post-transfusion symptomatic benefit, and pre-transfusion ECOG-PS and hemoglobin levels seem to be independent predictors of survival. Further studies are needed to develop validated measures of objective functional changes to evaluate the clinical impact of transfusions and to identify patients most likely to benefit from it.

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Thyroid Immune-Related Adverse Events Among Cancer Patients Treated With Combination of Anti-PD1 and Anti-CTLA4 Immune-Checkpoint Inhibitors: Clinical Course and Outcomes

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1729 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A847-A847

Author(s):

David T W Lui ◽

Chi Ho Lee ◽

Vikki Tang ◽

Carol H Y Fong ◽

Alan C H Lee ◽

...

Keyword(s):

Adverse Events ◽

Cancer Patients ◽

Advanced Cancer ◽

Immune Checkpoint ◽

Clinical Course ◽

Prognostic Significance ◽

Thyroid Function Tests ◽

Thyroid Disorder ◽

Advanced Cancer Patients

Abstract Introduction: Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among cancer patients treated with anti-PD1 and anti-PDL1 monotherapies. There are scanty data in the literature thus far about the clinical course and prognostic significance of thyroid irAEs in the routine clinical use of combination anti-PD1/anti-CTLA4 treatment in advanced cancer patients. We evaluated the clinical course and predictors of thyroid irAEs, in relation to outcomes of advanced cancer patients treated with combination anti-PD1/anti-CTLA4. Method: We conducted a territory-wide study and identified advanced cancer patients who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Patients were excluded if (i) they had a history of thyroid disorder or thyroid cancer, (ii) immune checkpoint inhibitor-related endocrinopathies occurred before the commencement of combination anti-PD1/anti-CTLA4, (iii) they were on concurrent tyrosine kinase inhibitor (TKI), (iv) baseline thyroid function tests (TFTs) were absent or abnormal, and (v) the duration of follow-up was <30 days. TFTs were monitored every three weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. The initial presentation was classified into hypothyroidism (overt if TSH >4.8 mIU/L and fT4 <12 pmol/L; subclinical if TSH >4.8 mIU/L and fT4 12-23 pmol/L) and thyrotoxicosis (overt if TSH <0.35 mIU/L and fT4 >23 pmol/L; subclinical if TSH <0.35 mIU/L and fT4 12-23 pmol/L). Results: One hundred and three patients were included (median age: 59 years; 71.8% men). Around half of patients had hepatocellular carcinoma. About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n=4; subclinical, n=2), and 11 with hypothyroidism (overt, n=2; subclinical, n=9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (OR 3.67, 95% CI 1.19-11.4, p=0.024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was associated with better overall survival (adjusted hazard ratio 0.39, 95% CI 0.19-0.79, p=0.009), independent of prior exposure to anti-PD1 (p=0.386) and prior TKI exposure (p=0.155). Conclusion: Thyroid irAEs are common in routine clinical practice among advanced cancer patients treated with combination anti-PD1/anti-CTLA4, and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.

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A Systematic Review of the Safety, Feasibility and Benefits of Exercise for Patients with Advanced Cancer

Cancers ◽

10.3390/cancers13174478 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4478

Author(s):

Nico De Lazzari ◽

Timo Niels ◽

Mitra Tewes ◽

Miriam Götte

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Cancer Patients ◽

Advanced Cancer ◽

Exercise Intervention ◽

Cochrane Library ◽

Controlled Trials ◽

Advanced Cancer Patients ◽

Exercise Interventions ◽

Positive Effects

Exercise therapy is a common supportive strategy in curative cancer treatment with strong evidence regarding its positive effects on, for example, cancer-related fatigue, health- related quality of life, and physical function. In the field of advanced cancer patients, knowledge about exercise as a useful supportive strategy is missing. The aim of this systematic review was to evaluate the feasibility and safety of exercise interventions as well as its effects on lowering the symptom burden. We included randomized controlled trials and nonrandomized controlled trials with advanced cancer patients receiving any type of exercise intervention. After an extensive literature search (in accordance to PRIMSA guidelines) in PubMed, Cochrane Library, and SPORTDiscus, 14 studies including 940 participants with different cancer entities were eligible. The results indicated the safety of exercise. In total, 493 participants received exercise interventions, with nine adverse events and no severe adverse events. The median recruitment rate was 68.33%, and adherence to exercise intervention was 86%. Further research with a high-quality and larger sample size is needed to clarify the potential of exercise with advanced cancer patients. Different advanced cancer entities have distinguished symptoms, and future research should construct entities-specific trial populations to figure out the best supportive exercise interventions.

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