Safety of Anlotinib Capsules Combined with PD-1 Inhibitor Camrelizumab in the Third-Line Treatment of Advanced Non-Small-Cell Lung Cancer and Their Effect on Serum Tumor Markers

Objective. To explore the safety of anlotinib capsules combined with the PD-1 inhibitor (camrelizumab) in the third-line treatment of advanced non-small-cell lung cancer (NSCLC) and their effect on serum tumor markers. Methods. 88 patients with advanced NSCLC treated in the Oncology Department of our hospital from December 2018 to December 2019 were selected as research subjects and randomly and equally split into the single treatment group (STG) and combined treatment group (CTG). The levels of serum tumor markers after treatment were detected in both groups, and the incidence of adverse reactions during treatment was recorded. Results. Compared with the STG, CTG achieved obviously higher total effective rate ( P < 0.05), lower total incidence of adverse reactions ( P < 0.05), lower levels of serum tumor markers and average CFS score ( P < 0.001), and higher average KPS score ( P < 0.001). Conclusion. Application of anlotinib capsules combined with the PD-1 inhibitor (camrelizumab) in the third-line treatment of advanced NSCLC can effectively reduce the levels of serum tumor markers and cancer fatigue degree of patients, with a better effect than that of simple anlotinib treatment. In addition, further research of the combined treatment is helpful to establish a better therapeutic regimen for patients with advanced NSCLC.

Safety and efficacy of ICI plus anlotinib vs. anlotinib alone as third-line treatment in extensive-stage small cell lung cancer: a retrospective study

Purpose The objective of this study was to evaluate the safety and efficacy of immune checkpoint inhibitor (ICI) plus anlotinib as third-line treatment in extensive-stage small cell lung cancer (ES-SCLC). Methods A total of 120 patients with ES-SCLC who were admitted to Shandong Cancer Hospital between January 2019 and December 2020 were retrospectively analyzed. They were divided into the observation group (n = 62) and the control group (n = 58) according to their different treatment plans. The observation group was given ICI plus anlotinib, while the control group was given anlotinib alone. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and disease control rate (DCR). An efficacy evaluation was carried out every 6 weeks. Univariate and multivariate analyses were performed to identify the prognostic factors. The main treatment-related adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Results In the observation group and the control group, the DCRs were 87.1% and 72.4% (p = 0.044), and the ORRs were 19.4% and 6.9% (p = 0.045), respectively. The median PFS was longer in the observation group (7.5 months) than in the control group (4.6 months) (p = 0.0033). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score, brain metastases and metastatic sites were prognostic factors of ICI plus anlotinib. Compared with the control group, grade 1–2 immune-related pneumonia and hypothyroidism of patients in the observation group were significantly increased (p < 0.05), but grade 3–4 treatment-related adverse reactions were not significantly increased (p > 0.05). Conclusion ICI plus anlotinib showed promising efficacy and manageable toxicity in third-line treatment of ES-SCLC.

Comparison of Efficacy and Safety of Third-Line Treatments for Advanced Gastric Cancer: A Systematic Review With Bayesian Network Meta-Analysis

BackgroundAlthough various third-line treatments of advanced gastric cancer (AGC) significantly improved the overall survival, the optimal regimen has not been determined by now. This study aims to evaluate the efficacy and safety of multiple third-line treatments of AGC via integrated analysis and network meta-analysis (NMA) to provide valuable evidence for the optimal third-line systemic therapy for AGC.MethodsBy searching the databases of PubMed, Embase and the Cochrane Central Register of Controlled Trials from Jan 01, 2005 to Dec 31, 2020, we included phase II/III randomized clinical trials (RCTs) of the third-line treatments for AGC to perform NMA. The main outcomes for NMA were median overall survival (mOS), median progression-free survival (mPFS), disease control rate (DCR) and adverse events (AEs). We also included phase IB/II non-RCTs and II/III RCTs of the third-line immune checkpoint inhibitors (ICIs) for integrated analysis for pooled mOS (POS), pooled mPFS (PPFS) and other outcomes.ResultsEight phase II/III RCTs and 2 ICIs-related phase IB/II non-RCTs were included for analysis, involving 9 treatment regimens and 3012 AGC patients. In terms of mOS, apatinib (hazard ratio [HR] 0.61, 95% credible interval [CrI] 0.48-0.78) and nivolumab (HR 0.62, 95% CrI 0.51-0.76) were the most effective treatments compared with placebo. Apatinib also significantly improved mPFS versus placebo (HR 0.38, 95% CrI 0.29-0.49). Nivolumab ranked first among all regimens for 1-year OS rate and achieved the best OS in patients with HER-2 positive tumor, patients with gastroesophageal junction (GEJ) cancer and patients without gastrectomy history. TAS-102 (OR 7.46, 95% CrI 4.61-12.51) was the most toxic treatment in terms of AEs of grade 3 and higher (≥3 AEs). Pembrolizumab was more likely to cause immune related adverse event. Finally, the POS, pooled 1-year OS rate, pooled ORR and PPFS of AGC patients treated with third-line ICIs were 5.1 months, 25%, 10% and 1.71 months respectively.ConclusionsApatinib and nivolumab are the most effective treatments for the third-line treatment of AGC in contrast to the third-line chemotherapy. For AGC patients with HER-2 positive tumor, patients with GEJ cancer and patients without gastrectomy history, ICIs could be the optimal third-line treatment choice.

Pregabalin Attenuates Carboplatin-Induced Akathisia-Like Neuropathy: A Novel Case Report

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious adverse effects of chemotherapy. We experienced carboplatin (CBDCA)-induced akathisia-like CIPN, which was significantly attenuated by pregabalin administration, and report its treatment. A man in his 40s was administered CBDCA + pemetrexed (PEM) as the third-line treatment for recurrent malignant pleural mesothelioma. He rarely experienced mild akathisia-like symptoms on his feet before the diagnosis. The patient claimed that he exhibited mild degradation of the symptoms in the previous cisplatin (CDDP) + PEM treatment without the need for pharmacotherapy. Symptoms notably worsened approximately 7 days after the first cycle of CBDCA + PEM and did not disappear. Furthermore, symptoms worsened during the daytime and became milder at night. Lorazepam (0.5 mg) was administered 3 times a day from day 14 but was not effective. Finally, we evaluated the symptoms to be derived from CBDCA-induced neuropathy as he experienced the same symptoms in CDDP + PEM and did not have suspicious pathology or medicines for akathisia development. We decided to administer 75 mg pregabalin twice daily, resulting in significant symptom improvement. He also complained that he felt the symptoms 10 h after the previous pregabalin dose, suggesting that pregabalin was effective, and its effect weakened or disappeared as time progressed. Akathisia-like symptoms caused by CBDCA-induced CIPN are rare, but they significantly reduce the quality of life. Pregabalin was significantly effective in this case; therefore, we suggest that a detailed symptom interview and selection of the medicine, based upon the action mechanism, are necessary.

Safety And Efficacy of ICIs Plus Anlotinib Vs Anlotinib Alone As Third-Line Treatment In Extensive-Stage Small Cell Lung Cancer: A Retrospective Study

Purpose: The objective of this study was to evaluate safety and efficacy of Immune checkpoint inhibitors (ICIs) plus anlotinib as third-line treatment in extensive-stage small cell lung cancer (ES-SCLC).Methods: 120 patients with ES-SCLC admitted to Shandong Cancer Hospital between January 2019 and December 2020, were retrospectively analyzed. They were divided into observation group (n=62) and control group (n=58) according to different treatment plans. Observation group were given ICIs plus anlotinib, while control group were given anlotinib alone. The primary endpoint of the study was progression free survival (PFS), and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Efficacy evaluation was carried out every 2 cycles of the treatment. Univariate and multivariate analyses were performed to determine the prognostic factors. The main adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0.Results: In observation group and control group, the DCR were 87.1% and 72.4% (p = 0.044), and the ORR were 19.4% and 6.9% (p = 0.045), respectively. The median PFS was longer in observation group (7.53 months) than that in control group (4.57 months) (p = 0.0033). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score, brain metastases and metastatic sites were prognostic factors of ICIs plus anlotinib. Compared with control group, Grade 3-4 adverse events did not increase significantly in observation group. Treatment-related adverse events were tolerable and controllable.Conclusion: ICIs plus anlotinib showed promising efficacy and low toxicity in third-line treatment of ES-SCLC.

The Role of Anti-IgE Antibodies in Urticaria

Chronic urticaria, a common mast cell driven disease, has been considered so far an underestimated and difficult to treat disease, very often resulting in high physical, psychological and socio-economic burden. More than 60% of these patients are unresponsive to second generation H1 antihistamines, the first-line symptomatic treatment for urticaria. However, anti-IgE drugs (omalizumab and ligelizumab) showed improved activity in urticaria-treated patients with inadequate symptom control. Omalizumab has been widely proven to be very effective and well-tolerated in patients with antihistamine-refractory chronic spontaneous urticaria and inducible urticaria and is currently licensed for these indication as third-line treatment. Ligelizumab, a next-generation monoclonal anti-IgE antibody with higher affinity to IgE compared to omalizumab and a similar safety profile, has recently demonstrated to be even more effective than omalizumab. This review is focused on the role of anti-IgE antibodies in chronic urticaria.

Anti-PD-1 and regorafenib induce severe multisystem adverse events in microsatellite stability metastatic colorectal cancer: a case report

There exists a dilemma in the treatment of microsatellite stability (MSS) metastatic colorectal cancer (mCRC) owing to limited therapeutic options. Based on the promising results of the REGONIVO trial, combination of anti-PD-1 and regorafenib could be applicable for this kind of patients. Here we first report a case of an MSS mCRC patient who received sinitilimab plus regorafenib as third-line treatment and suffered severe multisystem treatment-related adverse events including Grade 3 myocarditis, myositis, myasthenia gravis, dermatitis, hepatitis, etc. Fortunately, all these adverse events have been reversed with administration of corticosteroids. Though evidence of tumor shrinkage was not found, CEA levels markedly decreased. Therefore, anti-PD-1 plus regorafenib might be optional for the MSS mCRC patients which requires special caution in the clinical practice.

Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. Methods: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. Results: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53–37.6) and the median follow-up duration was 40.83 months (range 11.33–88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.