Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group

Abstract Background Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. Methods We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). Results Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40–5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25–0.92, p = 0.026). Both parameters maintained their independent prognostic significance. Conclusions ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. Clinical trial identifier NCT04805099

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Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Cancers ◽

10.3390/cancers13061223 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1223

Author(s):

Daniel Pink ◽

Dimosthenis Andreou ◽

Sebastian Bauer ◽

Thomas Brodowicz ◽

Bernd Kasper ◽

...

Keyword(s):

Immune Checkpoint Inhibitors ◽

Median Overall Survival ◽

Phase Ii Trial ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Free Survival ◽

Safety And Efficacy ◽

Future Studies ◽

Entire Cohort

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

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The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

Cancer Biomarkers ◽

10.3233/cbm-210349 ◽

2021 ◽

pp. 1-11

Author(s):

Deniz Can Guven ◽

Oktay Halit Aktepe ◽

Melek Seren Aksun ◽

Taha Koray Sahin ◽

Gozde Kavgaci ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Multivariate Analyses ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Free Survival ◽

Patients With Cancer ◽

Early Progression ◽

Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

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Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm9051458 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1458 ◽

Cited By ~ 1

Author(s):

Fausto Petrelli ◽

Alessandro Iaculli ◽

Diego Signorelli ◽

Antonio Ghidini ◽

Lorenzo Dottorini ◽

...

Keyword(s):

Cancer Patients ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Free Survival ◽

Patients With Cancer ◽

Hazard Ratios ◽

The Cochrane Library ◽

Reporting Data

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumours treated with ICIs. PubMed, the Cochrane Library and Embase were searched from inception until September 2019 for observational or prospective studies reporting the prognoses of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI) and an HR > 1 associated with a worse outcome in ABs users compared to AB non-users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51–2.84; p < 0.01). Similarly, PFS was inferior in AB users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22–1.93; p < 0.01). In cancer patients treated with ICIs, AB use significantly reduced OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.

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Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.531 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 531-531

Author(s):

David James Pinato ◽

Ahmed Omar Kaseb ◽

Yinghong Wang ◽

Anwaar Saeed ◽

David Szafron ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Corticosteroid Treatment ◽

Free Survival ◽

Checkpoint Inhibitor Therapy ◽

The Impact

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received >10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

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Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis

10.20944/preprints202003.0425.v1 ◽

2020 ◽

Author(s):

Fausto Petrelli ◽

Alessandro Iaculli ◽

Diego Signorelli ◽

Antonio Ghidini ◽

Lorenzo Dottorini ◽

...

Keyword(s):

Cancer Patients ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Free Survival ◽

Patients With Cancer ◽

Hazard Ratios ◽

The Cochrane Library ◽

Reporting Data

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumors treated with ICIs. PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with a worse outcome in ABs users compared to no-ABs users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51–2.84; P<.01). Similarly, PFS was inferior in ABs users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22–1.93; p<.01). In cancer patients treated with ICIs, AB use significantly reduces OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.

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Effect of CMP, carfilzomib (CFZ) plus melphalan-prednisone (MP), on response rates in elderly patients (pts) with newly diagnosed multiple myeloma (NDMM): Results of a phase (Ph) I/II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8513 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8513-8513 ◽

Cited By ~ 3

Author(s):

Cyrille Touzeau ◽

Brigitte Kolb ◽

Cyrille Hulin ◽

Denis Caillot ◽

Lotfi Benboubker ◽

...

Keyword(s):

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Toxicity Profile ◽

Newly Diagnosed ◽

Efficacy Data ◽

Free Survival ◽

Safety And Efficacy ◽

Dose Limiting Toxicity ◽

Clinical Trial Information

8513 Background: MP+thalidomide (MPT) and MP+bortezomib (MPV) have shown significant progression-free survival and overall survival (OS) benefits in NDMM pts > 65 years (y) but are associated with peripheral neuropathy (PN). CFZ, a novel proteasome inhibitor, has shown promising activity and a favorable toxicity profile with low PN rates. Methods: This PhI/II study in NDMM >65y was designed to determine maximum tolerated dose (MTD) of CMP and assess safety and efficacy. In PhI, CFZ was started at 20mg/m2, then escalated to 27, 36, and 45mg/m2, given IV in 42-day (D) cycles (C) on D1/2/8/9/22/23/29/30 for 9C. Melphalan 9mg/m² and prednisone 60mg/m² were given PO D1–4 of every 45-day cycle. MTD was based on dose-limiting toxicity (DLT) in C1 defined as any grade (G) 4 hematologic adverse event (AE), any hematologic AE preventing aministration of ≥ 2 C1 CFZ doses except G4 thrombocytopenia without bleeding or G4 neutropenia ≤7D, ≥G3 febrile neutropenia, or any ≥G3 nonhematologic AE. Results: As of Jan 6, 2013, 24 pts have been enrolled in PhI: 6 for each dose level. There were 2 DLTs at 45mg/m2(fever, hypotension) resulting in a MTD of 36mg/m². In PhII, 45 additional pts received CMP at 36mg/m² CFZ for N=69 total PhI/II pts (median age 74y). ORR was 89% with 51% ≥VGPR. With median follow-up of 12 mo, the projected 2y OS was 89.9%. CMP was well tolerated without PN ≥G2. Conclusions: These results compare favorably to those of MPV, MPT, MP+lenalidomide (R), and R+dex in similar pts (ORR 71% San Miguel NEnglJMed2008, 76% Facon Lancet2007, 80% Palumbo JClinOncol2007 and 85% Rajkumar LancetOncol2010, respectively). CFZ 36mg/m2 +MP is tolerable and effective in elderly NDMM pts. Treatment is ongoing. Final safety and efficacy data will be presented during the meeting. Clinical trial information: NCT01279694.

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The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

Frontiers in Oncology ◽

10.3389/fonc.2021.704475 ◽

2021 ◽

Vol 11 ◽

Author(s):

Toshiya Fujisaki ◽

Satoshi Watanabe ◽

Takeshi Ota ◽

Kohei Kushiro ◽

Yusuke Sato ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Checkpoint Inhibitors ◽

Prognostic Significance ◽

Progression Free Survival ◽

Continuous Administration ◽

Free Survival ◽

Programmed Cell Death 1 ◽

Third Line ◽

Nsclc Patients

ObjectivesAlthough immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.MethodsWe retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.ResultsOf 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4–NE); p = 0.031].ConclusionThe current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

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Clinicopathological and Prognostic Significance of PRAME Overexpression in Human Cancer: A Meta-Analysis

BioMed Research International ◽

10.1155/2020/8828579 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jiaqiang Li ◽

Jianchun Yin ◽

Jianhua Zhong ◽

Zhilin Yang ◽

Aifa Tang ◽

...

Keyword(s):

Human Cancer ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Progression Free Survival ◽

Positive Lymph Node ◽

Clinicopathological Features ◽

Cancer Prognosis ◽

Free Survival ◽

Patients With Cancer

Numerous studies have demonstrated that preferentially expressed antigen in melanoma (PRAME) is abnormally expressed in various solid tumours. However, the clinicopathological features and prognostic value of the PRAME expression in patients with cancer remain unclear. Accordingly, we performed a meta-analysis to accurately assess the association of the expression level of PRAME with clinicopathological features and cancer prognosis. Relevant study collection was performed in PubMed, Web of Science, and Embase until 28 February 2020. A total of 14 original studies involving 2,421 patients were included. Our data indicated that the PRAME expression was significantly associated with tumour stage ( OR = 1.99 , 95% CI: 1.48–2.67, P < 0.001 ) and positive lymph node metastasis ( OR = 3.14 , 95% CI: 1.99–4.97, P < 0.001 ). Pooled results showed that overexpression of PRAME is positively correlated with poor disease-free survival ( HR = 1.60 , 95% CI: 1.36–1.88, P < 0.001 ), progression-free survival ( HR = 1.88 , 95% CI: 1.02–3.46, P = 0.042 ), metastasis-free survival ( HR = 1.86 , 95% CI: 1.05–3.31, P = 0.034 ), and overall survival ( HR = 1.75 , 95% CI: 1.53–1.99, P < 0.001 ). In summary, these data are suggesting that PRAME is tumorigenic and may serve as a prognostic biomarker for cancer.

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Safety and Efficacy of Procarbazine and Lomustine Chemotherapy as a Salvage Treatment for Recurrent Adult Glioma

10.21203/rs.3.rs-878192/v1 ◽

2021 ◽

Author(s):

Stephen Ahn ◽

Young Il Kim ◽

Ja Young Shin ◽

Jae-Sung Park ◽

Changyoung Yoo ◽

...

Keyword(s):

Electronic Medical Records ◽

Medical Records ◽

Progression Free Survival ◽

Potential Toxicity ◽

Eligibility Criteria ◽

Free Survival ◽

Safety And Efficacy ◽

Significant Difference ◽

Pcv Chemotherapy ◽

Adult Glioma

Abstract PurposeWhile procarbazine, lomustine, and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma, whether vincristine included in this regimen is beneficial is uncertain due to its potential toxicity and uncertain efficacy. In this study, we evaluated the safety and efficacy of PC chemotherapy in contrast with those of PCV chemotherapy. MethodsUsing electronic medical records, all patient with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary’s Hospital or St. Vincent’s Hospital were examined retrospectively. A total of 59 patients met our eligibility criteria. Among them, 15 patients received PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). ResultsThe PC group presented a significantly lower hematology toxicity (anemia: 6.7% vs. 45.5%; p = 0.02 and thrombocytopenia: 20.0% vs. 70.4%; p < 0.001). Also, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s), or total cessation of chemotherapy, were significantly less frequent (26.7% vs. 68.2%; p = 0.012). The overall survival of PC group was significantly longer than that of PCV group (396 vs. 232 days; p = 0.042), while there was no significant difference in progression-free survival between two groups (284.5 vs. 131 days; p = 0.077). ConclusionThis is the first comparative study to suggest that PC chemotherapy leads to less toxicity than PCV chemotherapy without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are needed to validate our findings. 

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