Comparison of time to failure of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy: a consecutive analysis of patients having NSCLC with high PD-L1 expression

Abstract Introduction There are two treatment strategies for non-small cell lung cancer (NSCLC) exhibiting a high expression level of programmed death-ligand 1 (tumor proportion score ≥ 50%): pembrolizumab plus chemotherapy and monotherapy. We retrospectively compared their efficacy and safety. Materials and methods We reviewed the efficacy and safety of first-line pembrolizumab-containing regimens administered between 2017 and 2020 to consecutive patients. The patients were divided into a pembrolizumab plus chemotherapy group (Combo group) or monotherapy group (Mono group). To compare the efficacy, we monitored the time to failure of strategy (TFS) defined as the time from the start of treatment to the occurrence of one of the following events: the addition of any drug not included in the primary strategy, progression of cancer after complete therapy, progression and no subsequent therapy, or death, whichever occurred first. We used the propensity score matching (PSM) to reduce the bias. Results A total of 126 patients were identified (89 in the Mono group and 37 in the Combo group). PSM matched 36 individuals from each of the two groups. The overall response rate and median progression-free survival of the Combo group were better than those of the Mono group. However, the median TFS was almost the same (11.3 months vs. 14.9 months; hazard ratio 1.40 [95% confidence interval 0.62–3.15]). The frequency of all serious adverse effects was higher in the Combo group than in the Mono group. Discussion Due to similar efficacy in TFS, both pembrolizumab plus chemotherapy and monotherapy are valid options for NSCLC.

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Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure

Blood ◽

10.1182/blood-2008-02-141614 ◽

2008 ◽

Vol 112 (12) ◽

pp. 4445-4451 ◽

Cited By ~ 127

Author(s):

Michael Wang ◽

Meletios A. Dimopoulos ◽

Christine Chen ◽

M. Teresa Cibeira ◽

Michel Attal ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Time To Progression ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Previously Treated ◽

Survival Studies

AbstractThis analysis assessed the efficacy and safety of lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma (MM) previously treated with thalidomide. Of 704 patients, 39% were thalidomide exposed. Thalidomide-exposed patients had more prior lines of therapy and longer duration of myeloma than thalidomide-naive patients. Lenalidomide + dexamethasone led to higher overall response rate (ORR), longer time to progression (TTP), and progression-free survival (PFS) versus placebo + dexamethasone despite prior thalidomide exposure. Among lenalidomide + dexamethasone-treated patients, ORR was higher in thalidomide-naive versus thalidomide-exposed patients (P = .04), with longer median TTP (P = .04) and PFS (P = .02). Likewise for dexamethasone alone-treated patients (P = .03 for ORR, P = .03 for TTP, P = .06 for PFS). Prior thalidomide did not affect survival in lenalidomide + dexamethasone-treated patients (36.1 vs 33.3 months, P > .05). Thalidomide-naive and thalidomide-exposed patients had similar toxicities. Lenalidomide + dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo + dexamethasone, independent of prior thalidomide exposure. Lenalido-mide + dexamethasone was superior to placebo + dexamethasone, independent of prior thalidomide exposure. Although prior thalidomide may have contributed to inferior TTP and PFS compared with thalidomide-naive patients, these parameters remained superior compared with placebo + dexamethasone; similar benefits compared with placebo + dexamethasone were not evident for thalidomide-exposed patients in terms of overall survival. Studies were registered at http://www.clinicaltrials.gov under NCT00056160 and NCT00424047.

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Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease

Cancers ◽

10.3390/cancers12041035 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1035 ◽

Cited By ~ 3

Author(s):

Xiang Zhou ◽

Patricia Flüchter ◽

Katharina Nickel ◽

Katharina Meckel ◽

Janin Messerschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Response Rate ◽

Treatment Strategies ◽

Progression Free Survival ◽

Serological Response ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Extramedullary Disease ◽

Heavily Pretreated ◽

Pretreated Patients

Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.

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A meta-analysis comparing regorafenib with TAS-102 for treating refractory metastatic colorectal cancer

Journal of International Medical Research ◽

10.1177/0300060520926408 ◽

2020 ◽

Vol 48 (7) ◽

pp. 030006052092640

Author(s):

Guan-Li Su ◽

Yuan-Yuan Wang ◽

Jin-Cheng Wang ◽

Hao Liu

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Odds Ratio ◽

Meta Analysis ◽

Progression Free Survival ◽

Similar Efficacy ◽

Efficacy And Safety ◽

Free Survival ◽

Hand Foot Syndrome

Objective We performed this meta-analysis to compare the efficacy and toxicity of regorafenib and TAS-102. Methods Electronic databases were searched to identify studies comparing the efficacy and safety of regorafenib and TAS-102 in patients with chemotherapy-refractory metastatic colorectal cancer using pooled analyses. Results Three clinical trials were included in this analysis. Regarding the reasons for treatment discontinuation, regorafenib was significantly associated with disease progression (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.21–0.50) and adverse events (OR = 4.38, 95% CI = 2.69–7.13). However, overall (OR = 0.97, 95% CI = 0.81–1.17) and progression-free survival (OR = 1.01, 95% CI = 0.86–1.18) did not significantly differ between the groups. The most common treatment-related adverse events in the regorafenib group were neutropenia (OR = 0.06, 95% CI = 0.03–0.11), hand–foot syndrome (OR = 50.34, 95% CI = 10.44–242.84), and liver dysfunction (OR = 34.51, 95% CI = 8.30–143.43). Conversely, the incidence of thrombocytopenia did not differ between the two groups. Conclusions Regorafenib and TAS-102 have similar efficacy but different adverse event profiles. Differences in the toxicity profiles of the two drugs will help guide treatment selection.

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The efficacy and safety of lenvatinib in the treatment of solid tumors: an up-to-date meta-analysis

Future Oncology ◽

10.2217/fon-2020-0327 ◽

2021 ◽

Author(s):

Wen jie Xie ◽

Shuai Zhang ◽

Lei Su ◽

Yan hong Li ◽

Xi Zhang ◽

...

Keyword(s):

Overall Survival ◽

Overall Response Rate ◽

Response Rate ◽

Meta Analysis ◽

Severe Infection ◽

Progression Free Survival ◽

Hazard Ratio ◽

Efficacy And Safety ◽

Free Survival ◽

Overall Response

Aim: We performed an updated meta-analysis to evaluate the efficacy and safety of lenvatinib in cancer patients. Materials & methods: Databases were searched to identify relevant trials. Data were extracted to evaluate overall survival, progression-free survival, overall response rate and grade ≥3 adverse events. Results: The pooled analysis demonstrated that lenvatinib significantly improved progression-free survival (hazard ratio: 0.43; 95% CI: 0.23–0.80; p = 0.008), overall survival (hazard ratio: 0.85; 95% CI: 0.75–0.97; p = 0.013) and overall response rate (relative risk: 6.89; 95% CI: 2.22–21.36; p = 0.001) compared with control therapy. However, the use of lenvatinib can increase the risk of severe infection. Conclusion: Lenvatinib-containing regimens are associated with better progression-free survival, overall survival and overall response rate, but can induce severe infection.

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Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

BMC Cancer ◽

10.1186/s12885-020-07614-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Mashiro Okunaka ◽

Daisuke Kotani ◽

Ken Demachi ◽

Akihito Kawazoe ◽

Takayuki Yoshino ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Progression Free Survival ◽

Similar Efficacy ◽

Hazard Ratio ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Free Survival ◽

Grade 3

Abstract Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9 months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P = 0.573). Median overall survival (OS) was 10.9 months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3 months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P = 0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC.

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Apatinib, a novel VEGFR-2 tyrosine kinase inhibitor, for relapsed and refractory nasopharyngeal carcinoma: data from an open-label, single-arm, exploratory study

Investigational New Drugs ◽

10.1007/s10637-020-00925-2 ◽

2020 ◽

Vol 38 (6) ◽

pp. 1847-1853

Author(s):

Ling Li ◽

Fei Kong ◽

Lei Zhang ◽

Xin Li ◽

Xiaorui Fu ◽

...

Keyword(s):

Overall Survival ◽

Nasopharyngeal Carcinoma ◽

Adverse Events ◽

Overall Response Rate ◽

Response Rate ◽

Kinase Inhibitor ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Open Label ◽

Free Survival

Summary Purpose Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has shown promising efficacy against several solid cancers, but evidence of its efficacy against relapsed and refractory nasopharyngeal carcinoma is limited. We investigated the efficacy and safety of apatinib for relapsed and refractory nasopharyngeal carcinoma in an open-label, single-arm, phase II clinical trial. Fifty-one patients with relapsed and refractory nasopharyngeal carcinoma in the First Affiliated Hospital, Zhengzhou University, who met the inclusion criteria were enrolled in the study. All patients received apatinib at an initial dose of 500 mg daily (1 cycle = 28 days). The primary and secondary endpoints were overall response rate, progression-free survival, and overall survival. We evaluated treatment effects and recorded apatinib-related adverse events by performing regular follow-ups and workup. The overall response rate (complete and partial responses) was 31.37% (16/51). The median overall survival and progression-free survival were 16 (95% CI, 9.32–22.68) and 9 months (95% CI, 5.24–12.76), respectively. Most patients tolerated treatment-related adverse events of grades 1 and 2; hypertension (29, 56.86%), proteinuria (25, 49.02%), and hand–foot syndrome (27, 52.94%) were the most common adverse events. There were no treatment-related deaths. Apatinib showed good efficacy and safety in patients with relapsed and refractory NPC.

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Efficacy and safety of ramucirumab containing chemotherapy in patients with pretreated metastatic gastric neuroendocrine carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.157 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 157-157

Author(s):

Saori Mishima ◽

Akihito Kawazoe ◽

Hiroshi Matsumoto ◽

Yasutoshi Kuboki ◽

Hideaki Bando ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Overall Response Rate ◽

Response Rate ◽

Advanced Disease ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Free Survival ◽

Unexpected Adverse Event ◽

Gastric Neuroendocrine Carcinoma ◽

Advanced Gastric Adenocarcinoma

157 Background: Gastric neuroendocrine carcinoma (G-NEC) is associated with poor prognosis. Most patients (pts) present with advanced disease and have short survival. Ramucirumab (RAM), a monoclonal antibody for VEGFR-2, has been effective for advanced gastric adenocarcinoma (AC). However, little is known about efficacy of RAM containing chemotherapy in G-NEC. Methods: We retrospectively analyzed and compared the efficacy and safety of RAM containing chemotherapy in pretreated G-NEC and AC pts in our hospital (March 2015- January 2017). G-NEC was defined by NEC features, regardless of the proportion, based on histology and neuroendocrine markers (synaptophysin, chromogranin A or CD56). VEGFR-2 expression in tumor vessels was evaluated in archival primary G-NEC tissues by immunohistochemistry using the same anti-VEGFR2 primary antibody and scoring scheme (vascular VEGFR2 H-score) as in REGARD trial (Fuchs CS, et al. BJC. 2016). Results: Seventeen G-NEC and 173 AC pts were analyzed. Therapy for G-NEC included RAM + paclitaxel (n = 13), RAM + irinotecan (n = 2), and RAM monotherapy (n = 2). The overall response rate was significantly better in pts with G-NEC than AC (59 vs. 22%, p = 0.001). Progression-free survival was significantly longer in pts with G-NEC than AC (median 6.8 vs. 3.2 months, HR 0.38 [95%CI 0.22-0.66]; p < 0.001). Overall survival was significantly longer in pts with G-NEC than AC (median 16.2 vs. 9.6 months, HR 0.4 [95%CI 0.19-0.86]; p = 0.014). No severe or unexpected adverse event occurred. Median vascular VEGFR2 H-score, based on available G-NEC tissues from 12 pts, was 220 (range 150-260) which was markedly higher than that reported on AC tissues from REGARD trial as historical control (median 35, range 0-240). Conclusions: Compared to AC patients, RAM containing chemotherapy showed a promising activity without severe or unexpected safety profile in G-NEC patients. This may in part be explained by higher vascular VEGFR-2 expression in G-NEC tissues. These data, though preliminary, support further clinical evaluation of RAM and biomarker investigation in this subset of gastric cancer.

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Anti-angiogenic Therapy for Advanced Primary Pulmonary Lymphoepithelioma-like Carcinoma: a Retrospective Multicenter Study

10.21203/rs.3.rs-1109138/v1 ◽

2021 ◽

Author(s):

Hejing Bao ◽

LingZhen Ma ◽

Mengge Yu ◽

Xiaoli Lin ◽

Chengzhu Zhao ◽

...

Keyword(s):

Progression Free Survival ◽

Research Data ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung ◽

Free Survival ◽

Angiogenic Therapy ◽

Median Progression Free Survival ◽

Retrospective Multicenter Study ◽

Better Than

Abstract Purpose: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients.Methods: Advanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy(AT group) or chemotherapy (CT group)alone.Results: A total of 65 patients were enrolled in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy, and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival in the AT group was 11.2 months [95% confidence interval (CI), 5.9-16.5], The median progression-free survival in the CT group was 7.0 months [95%CI, 5.1-8.9][Hazard Ratio (HR), 0.49; 95%CI, 0.29-0.83; P=0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The ORR of two groups were 45.2% (95% CI, 0.27 to 0.64), 38.2% (95% CI, 0.21 to 0.56), (P = 0.571). The DCR of two groups were 93.5% (95% CI, 0.84 to 1.03), 88.2% (95% CI, 0.77 to 1.00), (P = 0.756).Conclusions: Among patients with advanced PPLELC, the progression free survival of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.

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Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

10.21203/rs.3.rs-26226/v1 ◽

2020 ◽

Author(s):

Mashiro Okunaka ◽

Daisuke Kotani ◽

Ken Demachi ◽

Akihito Kawazoe ◽

Takayuki Yoshino ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Progression Free Survival ◽

Similar Efficacy ◽

Hazard Ratio ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Free Survival ◽

Grade 3

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Efficacy and safety of ramucirumab-containing chemotherapy in patients with pretreated metastatic gastric neuroendocrine carcinoma

ESMO Open ◽

10.1136/esmoopen-2018-000443 ◽

2018 ◽

Vol 3 (7) ◽

pp. e000443 ◽

Cited By ~ 2

Author(s):

Saori Mishima ◽

Akihito Kawazoe ◽

Hiroshi Matsumoto ◽

Yasutoshi Kuboki ◽

Hideaki Bando ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Vascular Endothelial ◽

Efficacy And Safety ◽

Free Survival ◽

Gastric Neuroendocrine Carcinoma ◽

Advanced Gastric Adenocarcinoma ◽

Endothelial Growth Factor

BackgroundRamucirumab (RAM), a monoclonal antibody for vascular endothelial growth factor 2 (VEGFR2), has been effective for advanced gastric adenocarcinoma (AC). However, little is known about the efficacy of RAM-containing chemotherapy (RAM-CTx) in gastric neuroendocrine carcinoma (G-NEC).MethodsWe retrospectively analysed and compared the clinical outcomes of patients (pts) with G-NEC receiving RAM-CTx, G-NEC receiving CTx without RAM and AC receiving RAM-CTx in our hospital. G-NEC was defined by neuroendocrine carcinoma features, regardless of the proportion, based on histology and neuroendocrine markers (synaptophysin, chromogranin A or CD56). VEGFR2 expression in tumour vessels was evaluated in archival primary G-NEC tissues by immunohistochemistry using the same anti-VEGFR2 primary antibody and scoring scheme (vascular VEGFR2 H-score) as in the REGARD trial.ResultsSeventeen G-NEC receiving RAM-CTx, 13 G-NEC receiving CTx without RAM and 173 AC pts receiving RAM-CTx were analysed. The overall response rate (59% vs 8 % vs 28%), progression-free survival (median 7.7 vs 1.8 vs 3.3 months) and overall survival (median 16.1 vs 8.6 vs 9.6 months) were significantly better in pts with G-NEC receiving RAM-CTx than G-NEC receiving CTx without RAM or AC receiving RAM-CTx. No severe or unexpected adverse events occurred. The median vascular VEGFR2 H-score, based on available G-NEC tissues from 12 pts receiving RAM-CTx, was 220 (range 150–260), which was markedly higher than that reported on AC tissues from the REGARD trial as historical control (median 35, range 0–240).ConclusionsRAM-CTx showed a promising activity without severe or unexpected safety profile in pts with G-NEC. This may in part be explained by higher vascular VEGFR2 expression in G-NEC tissues.

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