Treatment outcomes of recurrent and metastatic adenoid cystic carcinoma: A retrospective analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18056-e18056
Author(s):  
Julie Elaine McGrath ◽  
Punita Grover ◽  
Joanne Xiu ◽  
Chadi Nabhan ◽  
Jennifer Hsing Choe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adenoid Cystic Carcinoma ◽  
Real World ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
High Rate ◽  
Entire Cohort ◽  
Adenoid Cystic ◽  
Significant Difference

e18056 Background: Adenoid cystic carcinoma (ACC) is a rare malignancy of glandular tissue with a high rate of local recurrence and metastatic disease. Despite being regarded as an indolent disease, the clinical course of recurrent and metastatic ACC (R/M ACC) is highly variable. Responses to chemotherapy (chemo) are uniformly poor. Several multi-targeted tyrosine-kinase inhibitors (mTKIs), EGFR inhibitors (EGFRi) and other targeted agents have been studied in single-arm early phase trials with response rates ranging from 0-16% and progression free survival ranging from 2.5-17 months. However, there have been no comparative clinical trials and it is not known if one treatment strategy is superior. We undertook this retrospective study to assess the real-world clinical outcomes in patients with adenoid cystic carcinoma using the Caris Life Sciences database. Methods: Real world overall survival (rwOS) for cases of ACC was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of collection to the date of last contact. Cases were divided into subgroups based on treatment received – chemo (including platinum agents, taxanes, 5FU, topoisomerase inhibitors, anthracyclines), EGFRi (cetuximab, erlotinib, lapatinib), mTKIs (pazopanib, axitinib, sunitinib, cabozantinib, lenvatinib, sorafenib) and immune checkpoint inhibitors (ICIs) (atezolizumab, ipilimumab, pembrolizumab, nivolumab). Results: 368 patients (pts) were identified with ACC, 16 were locally recurrent and 216 tumors were taken from metastatic sites. 50 pts received chemo, 6 were treated with EGFRi and 15 with mTKIs. Pts who received combination EGFRi and chemo or mTKI and chemo were excluded. The median overall survival (mOS) all patients with metastatic ACC was 2.8 years (yrs). The mOS of pts with R/M ACC was 3 yrs for chemo, 2.9 yrs for EGFRi and 1.5 yrs for mTKIs. There was no significance in mOS between chemo vs mTKIs (HR 0.85, 95% CI 0.3 - 2, p = 0.72) and chemo vs EGFRi (HR = 0.88, 95% CI 0.3 - 2.5, p = 0.78). We further compared the outcomes of those treated with EGFRi (n = 8) with mTKIs (n = 19) in the entire cohort. For most pts, these agents were given as front line therapy. 25% (2/8) of patients had received treatment prior to EGFRi and 20% (4/9) prior to mTKIs (p = 1). There was no significant difference in mOS with HR 0.6 (95% CI 0.16 - 2.6), p = 0.6. We also compared the mOS of patients who received ICIs (n = 22) with those who did not (n = 346) but there was no significant difference (mOS 3.19 vs 3.17 yrs respectively, HR 0.87, 95% CI 0.47- 1.61, p = 0.65). Conclusions: There was no significant difference in the mOS between pts with R/M ACC who were treated with chemo, EGFRi or TKIs and in those who received ICIs compared to those who did not in our limited patient population. This highlights the need for predictive biomarkers for better patient selection with the goal of personalizing treatment strategies for this disease.

scholarly journals Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland

2021 ◽  
Vol 44 (1) ◽  
pp. E38-41
Author(s):  
Wenqian Chen ◽  
Andrea S. Fung ◽  
John B. McIntyre ◽  
Roderick Simpson ◽  
Arfan R. Afzal ◽  
...  
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Patient Characteristics ◽  
Outcome Data ◽  
Survival Outcomes ◽  
Immune Microenvironment ◽  
Adenoid Cystic ◽  
Kaplan Meier ◽  
Cluster Of Differentiation

Purpose: Early phase clinical studies are ongoing to evaluate the role of immune checkpoint inhibitors in adenoid cystic carcinoma (ACC) despite a paucity of information on the immune microenvironment. This study aims to better characterize the immune microenvironment of ACC tumours and evaluate survival outcomes based on tumour infiltrating lymphocyte (TIL) and programmed death-ligand 1 (PD-L1) expression. Methods: Patient characteristics, treatment and outcome data were collected for 24 ACC patients. The CD8+(cluster of differentiation 8) TIL and PD-L1 expression were quantified by immunohistochemistry. Marker expression and survival outcomes were evaluated by Kaplan-Meier analysis. Results: All cases were negative for PD-L1 expression; four cases had focal high, eight cases had focal moderate and 12 cases had low TIL expression. Based on TIL expression, there was no difference in disease-free or overall survival. Conclusion: Adenoid cystic carcinoma tumours were found to be associated with a poor immunogenic microenvironment, with absent PD-L1 expression and low CD8+ TILs. There was no association between TIL expression and survival. These data suggest that PD-L1 and TIL expression are unlikely to be useful as predictive biomarkers for response to immunotherapy.

scholarly journals Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

2021 ◽  
Author(s):  
Maaike Biewenga ◽  
Monique K. van der Kooij ◽  
Michel W. J. M. Wouters ◽  
Maureen J. B. Aarts ◽  
Franchette W. P. J. van den Berkmortel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Combination Therapy ◽  
Real World ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Negative Effect ◽  
Melanoma Patients

Abstract Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.

scholarly journals Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6290
Author(s):  
Hye-Won Lee
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Predictive Biomarkers ◽  
Effective Control ◽  
Extrinsic Factors ◽  
Medical Needs

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.

The Current Role of Immunotherapy in mCRPC: A Systematic Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Dalibey H ◽  
◽  
Hansen TF ◽  
Zedan AH ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Treatment Modalities ◽  
Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

scholarly journals Clinicopathological Features of Adenoid Cystic Carcinoma: An Institutional Perspective

2020 ◽  
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Head And Neck ◽  
Perineural Invasion ◽  
Neck Region ◽  
The Body ◽  
Clinicopathologic Features ◽  
Head And Neck Region ◽  
Adenoid Cystic ◽  
Significant Difference ◽  
Histologic Pattern

Introduction: Adenoid cystic carcinoma is a rare salivary gland malignancy that can occur in any part of the body, its clinicopathologic features are scarcely reported in locoregional literature. Therefore, in this study we aimed to evaluate the clinicopathologic features of adenoid cystic carcinoma in our population and to determine the association of age and site of its occurrence with histologic pattern and perineural invasion. Methods: We retrospectively analyzed 30 cases of adenoid cystic carcinoma that underwent surgical resections or biopsies from March 2009 to February 2020 at Liaquat National Hospital and Medical College, Karachi. Clinical and histopathological parameters including age, site, histological pattern and perineural invasion were determined and association between different parameters was analyzed. Results: Mean age of the patients was 30 + 16.1 years. Cribriform pattern was most common histologic pattern (63.3%) while head and neck region was the most common site of occurrence (83.3%). Perineural invasion which is one of the most important prognostic factors in adenoid cystic carcinoma was present in approximately half of the patients (46.7%). No significant association of age and site was found with histologic pattern and perineural invasion. Conclusion: Adenoid cystic carcinoma is a rare malignancy most commonly occurring in head and neck region with a high frequency of perineural invasion. No significant difference of histologic pattern and histologic prognostic parameter like perineural invasion was noted at different ages and different sites in our study.

An updated overall survival analysis with correction for protocol-planned crossover of the international, phase III, randomized, placebo-controlled trial of regorafenib in advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib (GRID).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 110-110 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Failure Time ◽  
Cox Model ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Primary Analysis ◽  
Significant Difference ◽  
The Impact

110 Background: The GRID study showed that regorafenib improves progression-free survival compared with placebo in patients with advanced GIST after failure of at least imatinib and sunitinib (HR 0.27; 1-sided p<0.0001; Demetri 2013). At the time of the primary analysis, no significant difference in the secondary endpoint of overall survival (OS) was observed (HR 0.77; p=0.199), but this result may have been confounded by the high rate of crossover to regorafenib (85%) of placebo patients at progression. We conducted exploratory analyses of updated OS data to assess the effect of correcting for this protocol-planned crossover. Methods: The data cut-off for this updated OS analysis was 31 January 2014 (2 years after the primary analysis). OS was corrected using two randomization-based methods: rank preserving structural failure time (RPSFT) and iterative parameter estimation (IPE); both methods are considered as best choice among all correction analytics. Hazard ratios and 95% CI were derived using the Cox model. Results: A total of 139 deaths had occurred at the time of data cut-off: 91 events (68.4% of patients) in the regorafenib group and 48 (72.7%) in the placebo group. A total of 22 patients remained on regorafenib treatment (median duration 2.1 years, range 0.9–2.4). The updated hazard ratio for OS favored regorafenib (0.85, 95% CI: 0.60 - 1.21; p=0.18). Median OS was estimated as 17.4 months in both groups, with crossover from placebo. The corrected HRs for OS are less than the uncorrected HR (Table). Conclusions: The updated analysis of OS in the GRID trial is consistent with the primary analysis. An exploratory analysis correcting for the impact of cross-over on OS suggests a survival benefit for regorafenib in GIST. Clinical trial information: NCT01271712. [Table: see text]

A randomized phase II study of durvalumab and tremelimumab compared to doxorubicin in patients with advanced or metastatic soft tissue sarcoma (MEDISARC, AIO-STS 0415).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS11075-TPS11075
Author(s):  
Viktor Grünwald ◽  
Sebastian Bauer ◽  
Barbara Hermes ◽  
Philipp Ivanyi ◽  
Lars H Lindner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Soft Tissue ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Soft Tissue Sarcomas ◽  
Predictive Biomarkers ◽  
Ecog Performance Status ◽  
Curative Intent

TPS11075 Background: Soft tissue sarcomas (STS) are rare tumors and exhibit substantial histological diversity. Efficacious targeted 1st line treatment for advanced or metastatic STS is not available, and the standard therapy has been anthracycline-based for decades. This strategy shows poor efficacy, as demonstrated by a median Overall Survival (OS) of 12-20 months. Several STS subtypes, however, have been shown to express PD-L1, and immune checkpoint inhibitors (ICI) have demonstrated principle anti-tumor activity in pretreated STS. Our ongoing clinical trial tests the activity and safety of ICI combination therapy in the first-line setting. We hypothesize that the dual checkpoint blockade with Durvalumab (PD-L1) and Tremelimumab (CTLA-4) improves overall survival in STS when compared to the standard of care doxorubicin. Methods: MEDISARC is a multi-center phase II trial that is enrolling adult treatment-naïve patients with histologically confirmed STS of intermediate or high grade (FNCLCC grade 2 or 3) not amenable to surgery with curative intent and ECOG performance status 0-2. Chemosensitive histologic STS are eligible. 100 patients will be randomized 1:1, stratified by ECOG status (0 vs. 1/2). Patients in the experimental arm are treated with fixed doses of durvalumab (1.5 g Q4W) and tremelimumab (75 mg Q4W for 3 cycles, then Q12W) until Progressive Disease (PD) or for a maximum of 12 months. Doxorubicin treatment in the standard arm is at 75 mg/m2 Q3W and limited to 6 cycles. OS is the primary endpoint. Secondary endpoints include 2-year OS rate, PFS, ORR according to conventional and modified RECIST 1.1, safety and tolerability and health-related quality of life (EORTC QLQ-C30). OS analysis may be performed when the required number of events (E=70) has been observed. All randomized and treated subjects will be included in the efficacy and safety analysis. The accompanying translational research aims to identify prognostic and predictive biomarkers in blood and tumor tissue. Enrollment of patients started in April 2018 and is ongoing. As of February 2019, 32 patients have been enrolled. The study is sponsored by AIO-Studien-gGmbH, Berlin, Germany. Clinical trial information: 2016-004750-15.

Real-world outcome study among patients with renal cell carcinoma (RCC) receiving checkpoint inhibitors (CPIs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16073-e16073
Author(s):  
Hemant Phatak ◽  
Ruth Kim ◽  
Ting Yu ◽  
Jill Dreyfus ◽  
Julie A. Gayle ◽  
...  
Keyword(s):  
Real World ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Healthcare Database ◽  
First Line Therapy ◽  
Comorbidity Burden ◽  
The Us ◽  
Look Back ◽  
Comorbidity Index ◽  
Discharge Database

e16073 Background: North America has one of the highest rates of RCC, and in 2018, 65,340 new cases were diagnosed in the US alone. Tyrosine kinase inhibitors have been a mainstay treatment for RCC. However, the first CPI, nivolumab, was approved by the FDA as a second-line treatment for RCC in late 2015 and as a first-line therapy in combination with ipilimumab in 2018. In this study, real-world outcomes in patients with RCC receiving CPIs were examined. Methods: An observational study was conducted from March 1, 2015, to December 31, 2017, using the Premier Healthcare Database, a hospital discharge database. Patients with RCC aged ≥18 years were identified by ICD-9/10 codes and were included if they received a CPI during the study period, irrespective of treatment line. Comorbidities were assessed in a 6-month look-back period commencing at the time of first CPI treatment and RCC diagnosis. 34 distinct immune-related adverse events (irAEs) were identified in a 90-day look-back period from time of the irAE to determine if patients had received a CPI during that time. Patients were followed for 90 days after the irAE to determine if CPI treatment was reinitiated. Results: During the study period, 1228 patients with RCC received a CPI, of whom 719 (59%) had ≥1 irAE. Approximately 95% of patients received nivolumab and the remaining 5% received an off-label CPI. At the time of initial CPI treatment, patients who experienced any irAE during the study period had a higher Charlson Comorbidity Index (5.1±3.2 vs 4.2±3.0; p < 0.001) and were more likely to be hospitalized on an emergent basis than those without an irAE (9.0% vs 5.1%; p = 0.005). Patients with an irAE also had a higher average number of previous immune-related or immunocompromised comorbid conditions (0.33±0.57 vs 0.12±0.36; p < 0.001). After experiencing an irAE, 65% of patients reinitiated a CPI within 90 days. Conclusions: The majority of RCC patients receiving a CPI, mostly anti-PD-1 agents, experienced an irAE, and patients with irAEs had a higher comorbidity burden than those without irAEs. Most patients with irAEs reinitiated CPI treatment within 90 days.

scholarly journals CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade

2020 ◽  
pp. 382-392 ◽  
Author(s):  
Michael T. Schweizer ◽  
Gavin Ha ◽  
Roman Gulati ◽  
Landon C. Brown ◽  
Rana R. McKay ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
High Rate ◽  
Gleason Grade ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Grade Group ◽  
Distinct Subgroup

PURPOSE Translational studies have shown that CDK12 mutations may delineate an immunoresponsive subgroup of prostate cancer, characterized by high neo-antigen burden. Given that these mutations may define a clinically distinct subgroup, we sought to describe outcomes to standard drugs and checkpoint inhibitors (CPI). PATIENTS AND METHODS Clinical data from consecutive patients with CDK12 mutations were retrospectively collected from 7 centers. Several clinical-grade sequencing assays were used to assess CDK12 status. Descriptive statistics included PSA50 response rate (≥ 50% decline in prostate-specific antigen from baseline) and clinical/radiographic progression-free survival (PFS). RESULTS Of 52 patients with CDK12-mutated prostate cancer, 27 (52%) had detected biallelic CDK12 alterations. At diagnosis, 44 (88%) had Gleason grade group 4-5, 52% had T3-T4, and 14 (27%) had M1 disease. Median follow-up was 8.2 years (95% CI, 5.6 to 11.1 years), and 49 (94%) developed metastatic disease. Median overall survival from metastasis was 3.9 years (95% CI, 3.2 to 8.1 years). Unconfirmed PSA50 response rates to abiraterone and enzalutamide in the first-line castration-resistant prostate cancer setting were 11 of 17 (65%) and 9 of 12 (75%), respectively. Median PFS on first-line abiraterone and enzalutamide was short, at 8.2 months (95% CI, 6.6 to 12.6 months) and 10.6 months (95% CI, 10.2 months to not reached), respectively. Nineteen patients received CPI therapy. PSA50 responses to CPI were noted in 11%, and PFS was short; however, the estimated 9-month PFS was 23%. PFS was higher in chemotherapy-naïve versus chemotherapy-pretreated patients (median PFS: not reached v 2.1 months, P = .004). CONCLUSION CDK12 mutations define an aggressive prostate cancer subgroup, with a high rate of metastases and short overall survival. CPI may be effective in a minority of these patients, and exploratory analysis supports using anti–programmed cell death protein 1 drugs early. Prospective studies testing CPI in this subset of patients with prostate cancer are warranted.

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