scholarly journals Investigative therapy for advanced esophageal cancer using the option for combined immunotherapy and chemotherapy

Immunotherapy ◽  
2020 ◽  
Author(s):  
Huan Wang ◽  
Tian-Tian Xuan ◽  
Ying Chen ◽  
Hui Yu ◽  
Tian-Tian Gu ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Stage Iv ◽  
Esophageal Cancer Patient ◽  
Line Treatment ◽  
Advanced Esophageal Cancer ◽  
First Line ◽  
Combined Immunotherapy ◽  
First Line Treatment

Aim: Advanced esophageal cancer has limited therapeutic options and a poor outcome. The efficacy of immunotherapy, as the first-line treatment of advanced esophageal cancer, is uncertain. Results: A stage IV advanced esophageal cancer patient received the first-line treatment with a combination of pembrolizumab and chemotherapy. Partial response (PR) was achieved after three cycles, and the efficacy was evaluated as stable after six cycles of immunochemotherapy and two cycles of maintenance monotherapy. Immune-related adverse events (irAEs) were not obvious. The patient was followed up till November 2019 when he died of gastrointestinal hemorrhage. Conclusion: The combination of an immune checkpoint inhibitor and chemotherapy is effective and safe for the initial treatment of advanced esophageal cancer. To confirm the evidence from this case, larger clinical trials are required in the future.

Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Liver Cancers ◽  
First Line Treatment

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]

Impact on second-line treatment after failure of immune checkpoint inhibitor (ICI) combination chemotherapy in extensive-disease small cell lung cancer: Experience of the Okayama Lung Cancer Study Group.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20590-e20590
Author(s):  
Yuka Kato ◽  
Taku Noumi ◽  
Kazuhiko Saeki ◽  
Kiichiro Ninomiya ◽  
Toshio Kubo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Extensive Disease ◽  
To Receive ◽  
First Line Treatment

e20590 Background: For patients with extensive-disease small cell lung cancer (ED-SCLC), amrubicin monotherapy is an important therapy in the treatment of recurrence, but there has been no adequate evaluation of how effective it actually is after failure of first-line chemotherapy including immune checkpoint inhibitor (ICI). Therefore, the purposes of this study are to determine the proportion of patients who received amrubicin monotherapy in the treatment of relapse after first-line treatment with ICI (arm A) and to investigate the efficacy of amrubicin therapy after arm A compared with after chemotherapy without ICI (arm B). Methods: Consecutive 40 pts with ED-SCLC NSCLC were retrospectively assessed who underwent ICI-containing chemotherapy (n = 19) or standard cytotoxic chemotherapy (n = 21) in the 1st-line setting between 2017 and 2020. Results: In arm A, 3 of 19 patients (16%) were still on first-line ICI maintenance therapy, 2 (2/19; 11%) had ICI treatment adverse events (interstitial pneumonia, cardiopulmonary arrest), and 1 patient could not receive second-line therapy due to a decrease in performance status (PS) to 3. In arm B, 11 of 21 patients (52%) did not receive amrubicin as second-line therapy, including 1 patient with worsening PS, 1 patient with adverse events (hematologic toxicity), 1 patient refusal, and 6 patients with combination of ICI and chemotherapy. 23 patients (arm A; 13 (57%), arm B; 10 (43%)) were able to receive amrubicin monotherapy, including 7 patients (6 cases vs 1 case) were sensitive relapses, and 16 (7 vs 9 cases) were refractory relapses. There was no significant difference in either PFS or survival after first-line treatment in 16 patients with refractory relapse who received amrubicin as second-line treatment (PFS: 4.8 vs 5.2 months, p = 0.51), (median survival after first-line treatment: 9.6 vs 12.8, p = 0.75). Conclusions: Patients who received ICI in the first-line treatment were fully eligible to receive amrubicin in the second-line treatment. The recurrence pattern tended to be sensitive relapse and we found that the efficacy of amrubicin in refractory relapse was not affected by the administration of ICI in the first-line treatment.

scholarly journals PD-1 Inhibitor Plus Chemotherapy Versus Chemotherapy for First-Line Treatment in Advanced Esophageal Cancer: A Systematic Review and Meta-Analysis.

2021 ◽  
Author(s):  
Yao Lu ◽  
Mengli Xu ◽  
Lulu Guan ◽  
Yalan Yang ◽  
Yu Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Advanced Esophageal Cancer ◽  
First Line ◽  
Chemotherapy Group ◽  
First Line Treatment

Abstract Background: Immunotherapy combined with chemotherapy has recently changed the first-line treatment of several cancers. We perform a systematic meta-analysis to assess the efficacy and safety of PD-1 inhibitor plus chemotherapy for first-line treatment in advanced esophageal cancer.Methods: Data were collected from eligible studies searched from PubMed, Web of Science, Cochrane Library, Embase, American society of clinical oncology (ASCO) and the European Society for Medical Oncology (ESMO). Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS), pooled odds ratio (OR) for objective response rate (ORR) and treatment-related adverse effects (TrAEs) were estimated to assess the efficacy and safety of PD-1 inhibitor plus chemotherapy versus chemotherapy. We performed several subgroup analyses to explore the variables on immunotherapy efficacy for esophageal cancer. The five-point Jadad scoring system and the bias risk assessment were used to evaluate the quality of studies, and sensitivity analyses were carried out to evaluate the robustness of the combined outcomes. Results: Seven records involving 3754 participants were selected in our study. Compared to chemotherapy group, the OS (HR=0.72; 95% CI: 0.66-0.78, P<0.01), PFS (HR=0.62; 95% CI: 0.57-0.68, P<0.01) and ORR (OR=2.07; 95% CI: 1.76-2.43, P<0.01) were significantly longer in PD-1 inhibitor plus chemotherapy group. The overall survival benefit was observed in patients regardless of histology or PD-L1 combined positive score (CPS). OS and PFS were generally consistent across subgroups by clinical features. In safety analyses, PD-1 inhibitor plus chemotherapy had significantly higher incidence of TrAEs (OR=1.85; 95% CI: 1.21-2.84, P<0.01), but there was no statistical difference in grade 3 or higher TrAEs (OR=1.24; 95% CI: 1.00-1.55, P=0.05).Conclusion: Compared with chemotherapy, PD-1 inhibitor plus chemotherapy has an improvement of anti-tumor activity and controllable TrAEs for first-line treatment of advanced esophageal cancer.

scholarly journals Immune Checkpoint Inhibitor in First-Line Treatment of Metastatic Renal Cell Carcinoma: A Review of Current Evidence and Future Directions

2021 ◽  
Vol 11 ◽  
Author(s):  
Iris Tung ◽  
Arvind Sahu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Rcc ◽  
First Line Treatment

The incidence of renal cell carcinoma (RCC) is rising and metastatic RCC carries a very poor prognosis. The treatment paradigm for metastatic RCC has shifted dramatically in the last decade with multi-targeted tyrosine kinase inhibitors (TKI) previously used as first-line treatment but its utility is limited by short-lived efficacy and rapid disease progression. The dysregulation of immune cells in the tumour microenvironment contributes to unregulated growth of RCC. Thus, the use of immune checkpoint inhibitors has become first-line treatment for metastatic RCC and has offered dramatic improvement in clinical benefit and survival. Treatment with immune checkpoint inhibitor in combination with TKI appears to be promising in offering even greater response rates. The treatment for metastatic RCC continues to evolve and ongoing advances with new targeted agents and biomarkers are needed to continue to improve prognosis in the future.

scholarly journals New First Line Treatment Options of Clear Cell Renal Cell Cancer Patients with PD-1 or PD-L1 Immune-Checkpoint Inhibitor-Based Combination Therapies

2020 ◽  
Vol 9 (2) ◽  
pp. 565 ◽  
Author(s):  
Marc-Oliver Grimm ◽  
Katharina Leucht ◽  
Viktor Grünwald ◽  
Susan Foller
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Line Treatment ◽  
First Line ◽  
Immune Mediated ◽  
First Line Treatment

In metastatic renal cell carcinoma (mRCC) the PD-1 immune-checkpoint inhibitor (ICI) Nivolumab became a standard second line treatment option in 2015 based on a significant improvement of overall survival compared to Everolimus. Current pivotal phase 3 studies showed that PD-1 ICI-based combinations were more efficacious than the VEGFR-TKI Sunitinib, a previous standard of care, leading to approval of three new regimens as guideline-recommended first-line treatment. Nivolumab plus Ipilimumab is characterized by a survival advantage, a high rate of complete response and durable remissions in intermediate and poor prognosis patients. Despite frequent immune-mediated side effects, fewer symptoms and a better quality of life were observed compared to Sunitinib. Pembrolizumab or Avelumab plus Axitinib were characterized by an improved progression-free-survival and a high response rate with a low rate of intrinsic resistance. In addition, Pembrolizumab plus Axitinib reached a significant survival benefit. The side effect profile is driven by the chronic toxicity of Axitinib, but there is additional risk of immune-mediated side effects of the PD-1/PD-L1 ICIs. The quality of life data published so far do not suggest any improvement regarding patient-reported outcomes compared to the previous standard Sunitinib. The PD-1/PD-L1 ICIs thus form the backbone of the first-line therapy of mRCC.

266 Tumour mutation burden (TMB) and efficacy outcomes in the phase III DANUBE study of advanced urothelial carcinoma (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A292-A292
Author(s):  
Sophie Wildsmith ◽  
Jill Walker ◽  
Anne L’Hernault ◽  
Weimin Li ◽  
Hannah Bye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Unresectable Stage ◽  
First Line Treatment

BackgroundThe phase III DANUBE study assessed the efficacy of the PD-L1 inhibitor durvalumab (D), alone or in combination with the CTLA-4 inhibitor tremelimumab (T), versus standard of care chemotherapy (SoC) for the first-line treatment of unresectable, locally advanced or metastatic UC. The study did not meet its co-primary endpoints of improving overall survival (OS) for D monotherapy vs SoC in patients with high tumor PD-L1 expression or for D+T vs SoC in the intention-to-treat population.1 TMB measurement in blood (bTMB) or tumour (tTMB) has been linked to improved efficacy with PD-1/PD-L1 inhibitors in UC and with D+T in non-small cell lung cancer,2 thus providing a rationale to explore TMB in the DANUBE trial.MethodsBaseline plasma samples from DANUBE were assessed for bTMB using the Guardant OMNI platform, while baseline tTMB was measured in formalin-fixed paraffin-embedded (FFPE) tumour samples using the FoundationOne CDx gene panel. Associations between progression-free survival (PFS) and median and landmark OS with bTMB and tTMB levels at various cutoffs were assessed as part of a pre-specified exploratory analysis. The data cutoff occurred on January 27, 2020.ResultsAmong 1032 patients randomised in DANUBE, 536 (51.9%) were evaluable for bTMB and 623 (60.4%) were evaluable for tTMB. For D vs SoC, bTMB and tTMB were not associated with OS or PFS at any cutoff. For D+T, stronger associations between bTMB and OS as well as PFS were observed with increasing bTMB cutoffs (table 1). At the bTMB cutoff ≥ 24 mut/Mb, 12-month OS rates were 76.7% for D+T and 54.3% for SoC, whereas for bTMB < 24 mut/Mb, 12-month OS rates were 53.4% for D+T and 51.2% for SoC. Similar trends for both OS and PFS were observed with tTMB (table 1).Abstract 266 Table 1Association between TMB and survival outcomes with D+TAssociation between TMB and survival outcomes with D+TConclusionsBoth bTMB and tTMB are potentially useful biomarkers for enriching responses to D+T in previously untreated, advanced UC. Neither bTMB nor tTMB was associated with better outcomes for D monotherapy. Cutoffs of 24 mut/Mb for bTMB and 10 mut/Mb for tTMB appear optimal for D+T in the setting of previously untreated, advanced UC.Trial RegistrationThe trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.ReferencesAstraZeneca. Update on phase III DANUBE trial for IMFINZI and tremelimumab in unresectable, stage IV bladder cancer [press release] March 6, 2020. [https://www.astrazeneca.com/media-centre/press-releases/2020/update-on-phase-iii-danube-trial-for-imfinzi-and-tremelimumab-in-unresectable-stage-iv-bladder-cancer-06032020.html]Rizvi NA, Cho BC, Reinmuth N, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: The MYSTIC phase 3 randomized clinical trial. JAMA Oncol. 2020:6:661–674.Ethics ApprovalThe study protocol was approved by the Ethics Board at each investigator’s institution.

Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy

2012 ◽  
Vol 30 (28) ◽  
pp. 3533-3539 ◽  
Author(s):  
Arnauld Verschuur ◽  
Harm Van Tinteren ◽  
Norbert Graf ◽  
Christophe Bergeron ◽  
Bengt Sandstedt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
High Risk ◽  
Pulmonary Metastases ◽  
Stage Iv ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

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