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

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.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  

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]


2021 ◽  
Vol 11 ◽  
Author(s):  
Iris Tung ◽  
Arvind Sahu

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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20590-e20590
Author(s):  
Yuka Kato ◽  
Taku Noumi ◽  
Kazuhiko Saeki ◽  
Kiichiro Ninomiya ◽  
Toshio Kubo ◽  
...  

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.


Immunotherapy ◽  
2020 ◽  
Author(s):  
Huan Wang ◽  
Tian-Tian Xuan ◽  
Ying Chen ◽  
Hui Yu ◽  
Tian-Tian Gu ◽  
...  

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.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18525-e18525
Author(s):  
Bhavik J. Pandya ◽  
Anna Hadfield ◽  
Bruno C. Medeiros ◽  
Samuel Wilson ◽  
Cat N. Bui ◽  
...  

e18525 Background: There is currently limited data on the quality-of-life (QoL) of patients with acute myeloid leukemia (AML) in the real-world setting. The objective of this analysis was to understand the impact of AML on patients receiving first-line treatment vs those who were relapsed/refractory to first-line treatment and therefore on later lines of therapy. Methods: The Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey involving 61 US hematologists/hemato-oncologists and their consulting AML patients, was conducted between February–May 2015. Physicians provided details on patient demographics and clinical information. Each patient was asked to complete both the EQ-5D-3L and Functional Assessment of Cancer Therapy Leukemia (FACT-Leu). Scores range from −1.09–1 (EQ-5D-3L) and 0–176 (FACT-Leu), where a higher score indicates a better QoL. Data from physician-completed record forms and corresponding patient self-completion forms on a matched sample of 75 patients were analyzed. Results: Of the patients who took part in the survey, 75% (n = 56) were receiving first-line treatment for AML and 25% (n = 19) were relapsed/refractory to first-line treatment and had progressed to later lines of therapy. The first-line patients had a mean age of 56.6 years and an average of 2.1 symptoms whereas the relapsed/refractory patients had a mean age of 56.9 years and an average of 2.4 symptoms, according to the physician. First-line patients may have a directionally better QoL scores than those on later lines of therapy, according to both the EQ-5D (0.75 and 0.71 respectively, P= .51) and the FACT-Leu (103.7 and 92.5 respectively, P= .098) measures. Results from the FACT-Leu-Physical Well-Being sub-domain show that relapsed/refractory patients were significantly more likely than first-line patients to be affected physically by their AML condition (13.0 and 17.6 respectively, P= .005). Conclusions: AML patients who have relapsed or become refractory to first-line treatment report worse QoL than those still on first-line treatments. These observational data shows a need for effective and tolerable treatments that can maintain or improve patients’ QoL, especially for patients with relapsed or refractory disease.


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