scholarly journals The combination of Tislelizumab and apatinib obtained complete remission for alpha-fetoprotein-producing gastric cancer with microsatellite stability: case report

Author(s):  
Jinyu Xiang ◽  
CongCong Wang ◽  
Wenjing Gong ◽  
Aina Liu ◽  
Ping Sun

Abstract BackgroundAlpha‑fetoprotein (AFP)‑producing gastric cancer (AFPGC) is a rare type of gastric cancer with high metastasis rate and poor prognosis. Despite substantial progress in the treatment of many solid tumors, there are no reports of the safety and effectiveness of immune checkpoint inhibitor (ICI) in combination with anti-angiogenesis in AFPGC patients with microsatellite stability (MSS).Case presentationThis is a case of a 69-year-old man who was diagnosed with metastatic AFPGC. After the progression of resistance to chemotherapy, Tislelizumab combined with apatinib was attempted, although the patient was microsatellite stable. With 3 cycles of combination therapy, a partial remission (PR, shrunk by 56%) was obtained, and the quality of life improved significantly. Surprisingly, after more than one year of continuous application of the above treatment regimen, both the primary and metastatic tumors in this patient eventually disappeared, which achieved complete remission (CR) without surgery. Following the combined treatment, the patient had a progression-free survival of more than 16 months and now is still in continue to benefit. ConclusionsThis is the first report that we are aware of on the effective treatment of AFPGC with Tislelizumab in combination with Apatinib. This provides a highly effective and tolerable therapeutic strategy for microsatellite-stabilized AFPGC.

Author(s):  
Fatma E. El-Khouly ◽  
Sophie E. M. Veldhuijzen van Zanten ◽  
Marc H. A. Jansen ◽  
Dewi P. Bakker ◽  
Esther Sanchez Aliaga ◽  
...  

Abstract Introduction This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG). Methods Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m2) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m2) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year. Dose-limiting toxicities (DLT) were monitored biweekly. Secondary progression free survival (sPFS) and overall survival (OS) were determined based on clinical and radiological response measurements. Quality of life (QoL) during treatment was also assessed. Results Between November 2011 and March 2018, nine patients with disease progression after initial radiotherapy were enrolled. Median PFS at start of the study was 7.3 months (range 3.5–10.0). In the first dose cohort, one patient experienced a DLT (grade III acute diarrhea), resulting in enrollment of three additional patients in this cohort. No additional DLTs were observed in consecutive patients receiving up to a maximum dose of 85 mg/m2. Median sPFS was 3.2 months (range 1.0–10.9), and median OS was 13.8 months (range 9.3–33.0). Overall QoL was stable during treatment. Conclusions Daily erlotinib is safe and well tolerated in doses up to 85 mg/m2 when combined with biweekly bevacizumab and irinotecan in children with progressive DIPG. Median OS of the study patients was longer than known form literature.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 135-135
Author(s):  
Kohei Shitara ◽  
Hiroki Hara ◽  
Naoki Takahashi ◽  
Takashi Kojima ◽  
Akihito Kawazoe ◽  
...  

135 Background: In the phase 1 REGONIVO study, regorafenib of 80 mg/day plus nivolumab showed manageable safety profiles and encouraging anti-tumor activity for advanced colorectal cancer (CRC) or gastric cancer (GC) with objective response rate (ORR) of 36% in CRC and 44% in GC (Fukuoka, et al. ASCO 2019). Updated efficacy results are presented. Methods: Enrolled patients (pts) received regorafenib plus nivolumab in a dose-finding phase to estimate the maximum tolerated dose (MTD). Additional pts were enrolled in a dose-expansion phase. Regorafenib of 80 to 160 mg was administered once daily for 21 on 7 days off with nivolumab 3 mg/kg every 2 weeks. The primary endpoint was dose-limiting toxicity (DLT) during cycle one to estimate the MTD and the recommended dose. PD-L1 combined positive score (CPS) was assessed using the anti–PD-L1 28-8 antibody. Tumor mutation burden (TMB) was measured using Oncomine tumor mutation load assay. Results: Fifty pts were enrolled (25 CRC; 25 GC) until October 2018 with median prior treatment line of 3. Efficacy results were updated as of September 1st 2019. One CRC pt was with MSI-high but all other pts were with MSS or MMR-proficient. Among the 20 pts (9 CRC and 11 GC) with objective response (40%), responses are still ongoing in 13 pts (7 CRC and 6 GC) and the median duration of response was not reached (NR). Median progression free survival (PFS) was 7.8 months in CRC (95% CI, 2.8- NR) and 5.5 months (95% CI, 2.6-10.2 months) in GC. One-year PFS rate was 41.7% in CRC and 22.4% in GC. Median overall survival (OS) was not reached in CRC (95% CI, 9.7-NR) and 12.1 months (95% CI, 5.2-NR) in GC. One-year OS rate was 68% in CRC and 55.3% in GC. No significant difference of PFS and ORR was observed in CRC according to PD-L1 and TMB. Conclusions: Encouraging anti-tumor activity of the combination of regorafenib plus nivolumab had been maintained with long-term follow-up. A randomized study for MSS CRC is under planning. Clinical trial information: NCT03406871.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4739
Author(s):  
Jalid Sehouli ◽  
Alexander Mustea ◽  
Guelten Oskay-Özcelik ◽  
Maren Keller ◽  
Rolf Richter ◽  
...  

In the single-arm non-interventional OTILIA study, patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IIIB–IV ovarian cancer received bevacizumab (15 mg/kg every 3 weeks for up to 15 months) and standard carboplatin–paclitaxel. The primary aim was to assess safety and progression-free survival (PFS). Subgroup analyses according to age were prespecified. The analysis population included 824 patients (453 aged <70 years, 371 aged ≥70 years). At data cutoff, the median bevacizumab duration was 13.8 months. Grade ≥3 adverse events (AEs), serious AEs, and AEs leading to bevacizumab discontinuation were more common in older than younger patients, whereas treatment-related AEs were less common. Median PFS was 19.4 months, with no clear difference according to age (20.0 vs. 19.3 months in patients <70 vs. ≥70 years, respectively). One-year OS rates were 92% and 90%, respectively. Mean change from baseline in global health status/quality of life showed a clinically meaningful increase over time. In German routine oncology practice, PFS and safety were similar to reported randomized phase 3 bevacizumab trials in more selected populations. There was no notable reduction in effectiveness and tolerability in patients aged ≥70 years; age alone should not preclude use of bevacizumab-containing therapy. ClinicalTrials.gov: NCT01697488.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 159-159
Author(s):  
Reo Sato ◽  
Masanori Tokunaga ◽  
Masahiro Watanabe ◽  
Shizuki Sugita ◽  
Akiko Tonouchi ◽  
...  

159 Background: The incidence of upper-third early gastric cancer (EGC) has been increasing in East Asia. Although total gastrectomy (TG) has been a standard treatment for upper-third EGC, proximal gastrectomy (PG) or distal gastrectomy (DG) can be indicated for some selected patients. Theoretically, the more we preserve stomach volume, the better postoperative quality of life will be. However, this issue is not fully investigated. The aim of this study was to clarify the most suitable procedure for upper-third EGC. Methods: This study included 187 patients who underwent TG (n = 20), PG (n = 138), or DG (n = 29) for cT1N0 upper-third gastric cancer between 2009 and August 2017. Surgical outcomes, including bodyweight change one year after the surgery, were retrospectively compared among surgical procedures. DG was generally selected if the distance between the esophagogastric junction (EGJ) and proximal margin of the tumor was more than 20 mm. PG was chosen if at least the distal half of the stomach could be preserved. Otherwise, TG was performed. Results: Background characteristics and proportion of laparoscopic approach were not different among the groups. The duration of surgery was not significantly different, but intraoperative blood losswas significantly less in DG than PG (19 vs. 39 g, p = 0.02). The incidence of Clavien-Dindo classification grade IIIa or more anastomosis-related complications was less frequent in DG (3.4%) than in PG (15.9%, p = 0.13) or TG (10%, p = 0.56), although the differences were not statistically significant. Albumin and hemoglobin levels one year after surgery were not significantly different among the groups. Bodyweight loss one year after surgery was less in DG (11.1%) than in PG (14.6%, p = 0.03) or TG (16.6%, p < 0.01). Conclusions: DG was a safe procedure with less bodyweight loss, and thus preservation of the EGJ should be considered for all patients with tumors at least 2 cm apart from the EGJ. If the distance between EGJ and tumor is less than 2 cm, PG or TG will be indicated. However, surgical outcomes between PG and TG in this study were not different, and therefore, further investigations including long term quality of life are necessary.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15508-e15508
Author(s):  
Qiwen Shen ◽  
Mingyun WANG ◽  
Xiaobao Peng ◽  
Siyi Tan ◽  
Jiaqi Xie ◽  
...  

e15508 Background: Apatinib is the first oral anti-angiogenic agent approved for the treatment of advanced gastric cancer in China. With the development of marketing promotion, the real world observation of the efficacy and prognostic factors analysis of apatinib become the urgent need for clinical decision. The aim of this study is to evaluate the efficacy and safety of apatinib in patients with advanced gastric cancer, and the association between some prognostic factors and clinical outcomes. Methods: We collected the data of 153 patients with advanced gastric cancer, who were treated with apatinib after failure of at least one regimen chemotherapy from December 2014 to June 2019. Treatment response, progression-free survival(PFS), overall survival(OS) and treatment-related adverse events were evaluated. Results: The median PFS for 153 patients was 3.1m (95% confidence interval, CI 2.863-3.337). The median OS was 6.0m (95% CI 4.392-7.608). Adverse events of grade 3 or above happened in 47.6 percent of patients and 61.7 percent of whom stopped treatment. Multivariate analysis showed that the number of metastatic sites was the independent factor simultaneously predicting DCR (disease control rate, P = 0.008) and OS (P = 0.007). Patients spending more than one year from diagnosis to treatment with apatinib had better DCR (P = 0.032) and longer PFS (P = 0.015). Liver metastasis (P = 0.007) and combined systemic therapy (P = 0.036) were significantly associated with DCR, but not associated with PFS or OS. Conclusions: Some patients with advanced gastric cancer can benefit from apatinib. This study help us to identify patients who has potential benefit from apatinib.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chongkai Fang ◽  
Jietao Lin ◽  
Tao Zhang ◽  
Jiajun Luo ◽  
Duorui Nie ◽  
...  

A vast majority of colorectal cancer (CRC) patients with microsatellite stability (MSS) or proficient mismatch repair (pMMR) are refractory to immunotherapeutic strategies. The current research focusses on the combined treatment strategies for identification and optimization in order to improve the efficacy of immunotherapy among patients with microsatellite stability (MSS), who account for the majority of metastatic colorectal cancer (mCRC) cases. mCRC patients harboring MSS and the BRAFV600E mutation show a worse prognosis and barely benefit from immunotherapy. In this report, we discuss the case of a mCRC patient with MSS and BRAFV600E mutation, who exhibited significant response to the combined treatment with nivolumab and bevacizumab, and has been exhibiting a progression-free survival (PFS) of more than 17 months. Our findings indicate that combined anti-angiogenic therapy can improve the efficacy of immunotherapy, which results in the prolong survival of the patient. This is a case report on MSS and BRAFV600E colorectal cancer which presents with a response to immunotherapy and anti-angiogenic therapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Liqun Zhang ◽  
Zhuo Wang ◽  
Jiawen Xiao ◽  
Zhiyan Zhang ◽  
Haijing Li ◽  
...  

Gastric cancer (GC) is one of the most common malignancies worldwide. Notably, patients with advanced GC have a poor prognosis and quality of life, prompting the need for further studies on its prognostic markers. Among these, albumin and D-dimer are often used as prognostic factors in the prediction of a variety of tumors. Moreover, the albumin to D-dimer ratio (ADR) may be an improved predictor of chemotherapy effect and survival compared to albumin and D-dimer alone, but few studies have investigated this issue. Thus, we explored the relationship between pretreatment ADR and prognosis in advanced GC treated with first-line chemotherapy. A total of 247 advanced unresectable GC patients treated with first-line chemotherapy were retrospectively included. The cut-off value for ADR was determined using the receiver operating characteristic (ROC) curve. The ADR had a cut-off value of 41.64. Compared to albumin and D-dimer alone, ADR had the highest area under curve (AUC) value (AUC = 0.730), followed by albumin (AUC = 0.659) and D-dimer (AUC = 0.719). Additionally, we found that patients with a low ADR (<41.64) had a lower disease control rate (77.9% vs. 92.5%, P < 0.01 ), shorter overall survival (OS) (271 vs. 389 days), and shorter progression-free survival (PFS) (118 vs. 192 days) than patients with a high ADR (≥41.64). Similar results were also found on subgroup analysis, and ADR was found to be an independent advanced GC prognostic factor on multivariate analysis (all P < 0.001 ). Low ADR was found to be correlated with poor therapeutic effects of chemotherapy and shortened OS and PFS. Therefore, pretreatment ADR may be a useful tool for predicting the effect of chemotherapy and prognosis in advanced GC patients treated with first-line chemotherapy.


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