Treatment response in the intact primary renal mass (P-Rmass) and its relationship to the overall response to treatment in patients with metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 329-329
Author(s):  
Hamid Emamekhoo ◽  
Hameem I Kawsar ◽  
Jens C. Eickhoff ◽  
Danubia Hester ◽  
Tristan Bice ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Outcome Data ◽  
Response To Treatment ◽  
Second Line ◽  
First Line ◽  
Radiographic Response ◽  
Systemic Treatments ◽  
The Impact

329 Background: With the approval of more effective systemic treatments (syst Rx) such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI), the impact of cytoreductive nephrectomy (CN) on response to Rx and survival remains unknown. The majority of patients (pts) previously enrolled in clinical trials have had radical nephrectomy (RN) or CN prior to syst Rx. Therefore, the response of the P-Rmass to ICIs and the effect of intact P-Rmass on response to syst Rx is not well described. Methods: A retrospective review of 209 pts with mRCC who were treated with ICI in the first or second-line was conducted. Following the appropriate regulatory process, collaborators from 5 US sites collected clinical, pathological, and outcome data via chart review. The response was investigator-assessed for all pts with at least one post-treatment scan or evidence of clinical progression after treatment initiation. Overall radiographic response (ORR) includes complete response (CR) and radiographic response (Rad-resp) to treatment. Disease control rate (DCR) includes CR, Rad-resp, and stable disease. Results: Median age at diagnosis was 63 yrs and 69% were male. 102 pts (49%) had localized disease at diagnosis and underwent radical or partial nephrectomy, 3 (1%) had ablation/radiation of P-Rmass, 26 (12%) had CN, 9 (4%) had CN after an excellent response to syst Rx, 12 (6%) had a previous nephrectomy but developed a new Rmass (measurable target lesion), and 57 (27%) did not have CN and had an intact P-Rmass. 176 (84%) pts had clear cell histology. 27 (14%) and 23 (12%) had known sarcomatoid and rhabdoid features, respectively. Overall, 77 (37%) pts had a measurable Rmass while receiving syst Rx. 84 (40%), 93 (45%), and 10 (5%) pts received ICI (Ipilimumab/Nivolumab or Nivo), TKI, or Pembrolizumab/Axitinib in the first-line. 143 (68%) and 70 (33%) pts received second- and third-line treatment. 103 (72%) and 28 (19%) pts received ICI and TKI in the second-line, respectively. The best ORR and the Rad-resp in the intact P-Rmass in evaluable pts are summarized in the table below. ORR to ICI in the first or second-line were numerically higher in pts with an intact P-Rmass compared to pts who had nephrectomy, but this difference was not statistically significant (p= .38 and .35 respectively). Conclusions: The intact P-Rmass had a good response (62-70%) to the first-line syst Rx. Although the overall Rad-resp rates to ICI are numerically higher in pts with intact P-Rmass, this difference was not statistically significant. [Table: see text]

scholarly journals Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2312
Author(s):  
Henner Stege ◽  
Maximilian Haist ◽  
Michael Schultheis ◽  
Maria Isabel Fleischer ◽  
Peter Mohr ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Checkpoint Inhibitors ◽  
Patient Characteristics ◽  
Complete Response ◽  
Second Line ◽  
Treatment Cessation ◽  
Durable Response ◽  
Ongoing Treatment ◽  
Number Of Patients ◽  
The Impact

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.

scholarly journals Timing of immune checkpoint inhibitors for metastatic patients over 75 years of age: the earlier the better

2020 ◽  
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Kader Chouahnia ◽  
Virginie Fossey-Diaz ◽  
Stéphane Culine
Keyword(s):  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Significant Difference ◽  
Line Setting ◽  
The Impact

Abstract Background The impact of ageing on Immune Checkpoint Inhibitors (ICIs) effectiveness remains controversial. However, data from clinical studies do not show any difference between patients over 65 years and those under 65 years. We focused our study on patients over 75 and looked at the potential impact of timing in the use of ICIs. Methods We performed a meta-analysis of published randomized control trials (RCTs) concerning ICIs versus standard therapy in patients with advanced solid tumors. Overall Survival (OS) among the older (≥75 years) was compared with that of younger patients (< 75 years). Hazard ratios (HRs) with their 95% confidence interval (CI) were collected and pooled. Results Fifteen phase III studies evaluating anti-PD-1(nivolumab or pembrolizumab), anti-PD-L1 (atezolizumab or avelumab) or anti-CTLA-4 (ipilimumab) were included. Patients were enrolled for Non-Small-Cell-Lung-Cancer, Renal-Cell-Carcinoma, Melanoma, Head-and-Neck-Squamous-Cell-Carcinoma or Gastric Cancer. Eight studies assessed treatment in first-line setting and seven in the second line. The median age was 64 years, with 906 patients over 75 years of age and 5233 youngers. In first-line setting, HRs for death were 0.78 (95% CI: 0.61-0.99) in patients ≥75 years versus 0.84 (95% CI: 0.71-1.00) in younger. In second line setting, HRs for death were 1.02 (95% CI: 0.77-1.36) in patients ≥75 years versus 0.68 (95% CI: 0.61-0.75) in younger with a statistically significant difference observed between subgroups (p interaction = 0.009). Conclusions ICIs appears to be effective in patients over 75 years of age. However, the survival benefit is mainly observed in first-line treatment.

scholarly journals Beyond First-Line Immune Checkpoint Inhibitor Therapy in Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Rohini Sharma ◽  
Leila Motedayen Aval
Keyword(s):  
Immune Checkpoint ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hepatocellular Cancer ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Second Line ◽  
Research Strategies ◽  
First Line ◽  
Line Setting

Until recently, the treatment landscape for hepatocellular cancer (HCC) was dominated by tyrosine kinase inhibitors (TKIs) which offered an overall survival (OS) benefit when used both in the first-and second-line setting compared to best supportive care. However, the treatment landscape has changed with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of HCC with significant improvement in OS and progression free survival reported with combination atezolizumab and bevacizumab compared to sorafenib in the first-line setting. Nonetheless, the response to ICIs is 20–30% and invariably patients will progress. What remains unclear is which therapeutics should be used following ICI exposure. Extrapolating from the evidence base in renal cell carcinoma, subsequent therapy with TKIs offers both a response and survival benefit and are recommended by European guidelines. However, there are a number of novel therapies emerging that target mechanisms of ICI resistance that hold promise both in combination with ICI or as subsequent therapy. This paper will discuss the evidence for ICIs in HCC, the position of second-line therapies following ICIs and research strategies moving forward.

Is there a benefit of immune checkpoint inhibitors for patients over 75 years of age with advanced cancer in first and second line setting: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12031-12031 ◽  
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Christos Chouaid ◽  
Jean F. Morere ◽  
Kader Chouahnia ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Line Setting ◽  
The Impact

12031 Background: The impact of aging on Immune Checkpoint Inhibitors (ICIs) effectiveness is controversial. Currently, data from clinical studies do not show any difference between patients over 65 years and those under 65 years. We propose to compare the clinical benefit of ICIs in those over 75 and in those under 75. Methods: We performed a meta-analysis of published randomized control trials (RCTs) concerning ICIs versus standard therapy in patients with advanced solid tumours. Overall Survival (OS) among the older (≥75 years) was compared with that of younger patients ( < 75 years) in first and second line setting. Hazard ratios (HRs) with their 95% confidence interval (CI) were collected from the studies and pooled. Results: Fifteen phase III studies evaluating anti-PD-1 (nivolumab or pembrolizumab), anti-PD-L1 (atezolizumab or avelumab) or anti-CTLA-4 (ipilimumab) were included. Patients were enrolled for Non-Small-Cell-Lung-Cancer, Renal-Cell-Carcinoma, Melanoma, Head-and-Neck-Squamous-Cell-Carcinoma or Gastric-Cancer. Eight studies assessed treatment in first line setting and seven in second line. The median age was 64 years, with 906 patients over 75 years of age and 5233 younger. In first line setting, HRs for death were 0.78 (95% CI: 0.61-0.99) in patients ≥75 years versus 0.84 (95% CI: 0.71-1.00) in younger. In second line setting, HRs for death were 1.02 (95% CI: 0.77-1.36) in patients ≥75 years versus 0.68 (95% CI: 0.61-0.75) in younger with a statistically significant difference observed between subgroups (p interaction = 0.009). Conclusions: ICIs appears to be effective in patients over 75 years of age. However, the survival benefit comes mainly from the first line of treatment. This result encourages the use of ICIs early in the therapeutic management of patients over 75 years of age.

scholarly journals Second-Line Therapies in the Changing Landscape of First-Line Therapies for Metastatic Clear Cell Renal Cell Cancer

ONCOLOGY ◽  
2021 ◽  
pp. 306-310
Author(s):  
Tiffany Shaw ◽  
Hannah Lee ◽  
Robert Figlin
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Single Agent ◽  
Current Data ◽  
Treatment Modalities ◽  
Second Line ◽  
First Line ◽  
Line Setting

In recent years, first-line therapies for metastatic renal cell carcinoma (mRCC) have shifted to a combination of immune checkpoint inhibitors or a combination of antiangiogenesis tyrosine kinase inhibitors (TKIs) and immunotherapy. This has led to a need to address standard-of-care treatment in the second-line setting. Our review presents an analysis of current and upcoming data to guide treatment decisions. After progression on nivolumab plus ipilimumab, current data favor monotherapy TKI with cabozantinib or axitinib. Current literature for second-line therapy given after combination TKI plus immunotherapy shows the strongest evidence for either single-agent cabozantinib or combination everolimus with lenvatinib. Investigations are ongoing for the role of TKIs with immunotherapy in the second-line setting. Novel agents, such as HIF2α inhibitors, are currently being studied as single agents and in combination with other treatment modalities in efforts to improve patient outcomes in mRCC.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

Patients with steroid-refractory toxicity following immune checkpoint inhibitors: Frequent hospitalizations and long duration of illness.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2655-2655
Author(s):  
Mia Bothwell ◽  
Aaron Cheng ◽  
Leyre Zubiri ◽  
Meghan Mooradian ◽  
Yevgeniy R. Semenov ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Academic Medical Center ◽  
Complete Response ◽  
Second Line ◽  
Duration Of Illness ◽  
Long Duration ◽  
Steroid Refractory

2655 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer with significantly improved outcomes, but these agents have a unique spectrum of toxicities known as immune-related adverse events (irAEs). The recommended treatment for non-endocrine toxicities is steroid based. However, a subset of patients (pts) is steroid-refractory and requires second-line immunosuppression. There is very little evidence regarding this population. In this retrospective study we report the 1) incidence 2) type of treatment used 3) natural history and 4) potential predictors of steroid-refractory irAE at a major academic medical center. Methods: The Research Patient Database Registry at Mass General Brigham was used to identify pts treated with an ICI from 1/5/2017 to 6/1/2019. Pharmaceutical records identified a subset of the cohort received a second-line immunosuppressive agent within a 15-month period after ICI. For pts with steroid-refractory irAE additional information was collected: demographics, ICI regimen, type/#/and severity of irAE, clinical characteristics, # of admissions, length of stay (LOS), amount and duration of steroid therapy, second line immunosuppression type, treatment discontinuation rates, response, and outcome of re-challenge. Multivariate logistic regressions were used to predict risk of refractory toxicity and study the association of different variables (age, sex, race, marital status, cancer and ICI types) with refractory toxicities. Results: We identified 61 pts (1.4%) with steroid-refractory irAEs (48 colitis, 4 myocarditis, 6 pneumonitis, 3 neurologic) out of the total ICI cohort (N=4,325). 60.7% received ICI monotherapy. 24.6% received ICI in the adjuvant setting. Median length of steroid duration was 68 days with max of 1135 days. Despite use of second line immunosuppression, 25.8% of pts were never able to discontinue steroids. Majority of pts (72.1%) had at least one hospitalization with median LOS of 7.5 days. 93.4% of pts permanently discontinued the ICI responsible for the irAE. Thirteen pts (21.3%) were later re-challenged with ICI and 7 (53.8%) of these developed a subsequent irAE. Anti-CTLA-4 therapy was associated with a 10-fold risk of refractory toxicity compared to PD-1 (p<.05). Best tumor response was complete response in 21.3% and partial response in 26.2%. Among different cancer types, melanoma was most strongly associated with refractory events (OR 2.97 in comparison to thoracic malignancy). Conclusions: Refractory toxicity is uncommon but leads to high rates of ICI discontinuation, frequent hospitalizations, and a long duration of illness with exposure to prolonged and high-doses of steroids. There is an urgent need for further investigation into predictive factors for steroid-refractory toxicity given that ICI is being used more frequently and in earlier lines of treatment.

scholarly journals Treatments of Advanced Non‑Small Cell Lung Cancer (NSCLC) in an Italian Center: Drug Utilization and the Treatment Costs of Innovative Drugs

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Francovito Piantedosi ◽  
Raffaela Cerisoli ◽  
Ciro Battiloro ◽  
Francesca Andreozzi ◽  
Fabiana Vitiello ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line

AIM: To provide an updated picture of the therapies most commonly used in the advanced Non-Small Cell Lung Cancer (NSCLC) setting, together with the relevant costs.METHODS: This study considered the clinical records of patients affected by stage IIIb and IV NSCLC treated in the AORN dei Colli - Plesso Monaldi in Naples during the period January 2016-July 2017 and diagnosed since 2014, as well as the pathology lab database. Multivariate analyses were performed in order to identify the main predictors of time to next treatment and the main cost drivers.RESULTS: Data were collected on 575 patients, who were mainly affected by adenocarcinoma (62%) and squamous cell carcinoma (34%). 64% of patients were reported having been tested for molecular biomarkers (among the patients tested, 13% were EGFR+, 4% Alk t, and 1% ROS1 t). In accordance with the international guidelines, chemotherapy – as single agent or platinum-based doublets – was the prevalent first-line treatment, except among EGFR+ and ROS1 t patients, for whom the target therapy was authorized as first-line therapy. As second-line treatment, the target therapy and immune checkpoint inhibitors (nivolumab) were the most commonly used treatments. Drug expenditure per patient was remarkably higher in mutated patients (€ 29,053) versus wild-type patients, or patients with unknown mutational status (€ 11,854), who received just chemotherapy. The costs sustained in 2017 are proportionally higher than those sustained in 2016, mainlydue to the increasing eligibility to target therapy and immune checkpoint inhibitors and the wider biomarker analysis performed. From multivariate analyses, among the predictors of a longer time to next treatment (TTNT) were a better performance status and target therapy both in first and second line. The therapy for squamous cell carcinoma and other nonadeno histotypes turned out to be less expensive in patients treated just in the first line than that for adenocarcinoma and adenosquamous carcinoma. The use of immune checkpoint inhibitors in the second line results in increased costs compared to the use of chemotherapy. Also the target therapy in the first line results in an increase in the total costs with respect to chemotherapy in patients who received just a first-line therapy.CONCLUSIONS: Generally, in this study population, the treatments administered are in accordance with the international guidelines. The costs borne by the Health Systems are higher for the target therapy and the immune checkpoint inhibitors.

Possible immunologic predictors of the PD-1/PD-L1 checkpoint inhibitors' efficiency in lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21035-e21035
Author(s):  
Elena Yu. Zlatnik ◽  
Oleg I. Kit ◽  
Elena S. Bondarenko ◽  
Aleksandr B. Sagakyants ◽  
Maria A. Teplyakova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Partial Response ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Response To Treatment ◽  
Cell Mediated Immunity ◽  
Initial Amount ◽  
Lung Cancer Patients ◽  
Effect Of Therapy ◽  
Check Point Inhibitors

e21035 Background: Immunotherapy with PD-1/PD-L1 check-point inhibitors (CPI) is a new trend in oncology. Their effect significantly depends on the patients` immune status. The aim of the study was to search the immunologic parameters of lung cancer (LC) patients receiving immunotherapy as factors that could predict their effect. Methods: 20 patients (12 male and 8 female) with LC had adenocarcinoma – 15 (75%), squamous cell carcinoma – 5 (25%). PD-1/PD-L1 CPI were used: 9 patients received atezolizumab (43%), 9 (43%) – pembrolizumab and 3 (14%) – nivolumab. The effect of therapy was evaluated according to imRECIST v.1.1. Factors of cell-mediated immunity were assessed by flow cytometry before treatment including immunotherapy. CD8+CD279+, CD4+CD279+, TLR2, TLR4, TLR3, TLR8 were studied. Results: Complete response was observed in 2 (9%) patients, partial response in 5 (24%), stabilization in 4 (19%) and progression in 8 (38%). In one patient the treatment was cancelled due to the development of immune-mediated complication (Guillain-Barre syndrome). The factors studied varied depending on different effect. In cases of LC stabilization/progression the initial amount of CD8+CD279+ cells were twice lower than in cases with complete/partial response. In the first group CD8+CD279+ cells` level before the treatment was 0,1-3,4%, while in the other group 4,1-9% (7,0±1,16%). In patients with stabilization/progression CD4+CD279+ cells` level before the immunotherapy was 0,1-3,3 and in patients with response to treatment 1,4-7,8% (3,4±0,8%) of total CD4+ lymphocytes. Besides, the LC patients with different effect of treatment had different initial amount of CD4+ Tem cells: stable response to CPI developed in patients with their higher levels (40,8±3,9%) vs 15,3±3,9% in cases of tumor progression (p < 0.05). Initial high expression of TLR2 and TLR4 as well as low expression of TLR3 and TLR8 on monocytes in patients with response to immunotherapy suggests the contribution of innate immunity to its effect. Conclusions: Complete or partial response should be expected in cases of initially high per cent of T lymphocytes (CD4+, CD8+) CD4+ Tem cells and TLR2+, TLR4+ as well as low amount of TLR3+ and TLR8+ monocytes. These factors should be studied in future as predictive factors for effectiveness of CPI.

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