IMMUNOTHERAPY FOR NSCLC: THE RIGHT TREATMENT FOR THE RIGHT PERSON

2019 ◽  
Vol 65 (1) ◽  
pp. 27-41
Author(s):  
Yelena Artamonova
Keyword(s):  
Life Expectancy ◽  
Tumor Cells ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Combination Group ◽  
Line Treatment ◽  
Phase 3 ◽  
Median Response ◽  
The Right ◽  
High Level

Lung cancer is the leading cause of mortality from malignant tumors all over the world. Since most patients at the time of diagnosis already have stage III-IV of the disease, the search for new effective treatment strategies for advanced NSCLC is the most important problem of modern oncology. The results of the study of the anti-PD1 monoclonal antibody pembrolizumab were a real breakthrough in the treatment of NSCLC. In the KEYN0TE-001 study, the expression of PD-L1 on tumor cells was validated as a predictive biomarker of the drug's efficiency. Pembrolizumab demonstrated the possibility of achieving long-term objective responses, and a 4-year 0S with all histological types in the subgroup of pre-treated patients with PD-L1 expression> 50% was 24.8% and 15.6% in the PD-L1> 1% group. In a phase 2/3 randomized study KEYN0TE-10 in the 2nd line treatment of NSCLC with PD-L1 expression > 1% pembrolizumab significantly increased life expectancy compared to docetaxel and confirmed the possibility of longterm duration of objective responses, even after cessation of treatment. Then the focus of research shifted to the 1st line of treatment. About 30% of patients with NSCLC have a high level of PD-L1 expression on tumor cells and demonstrate the most impressive response to pembrolizumab therapy. A randomized phase 3 study KEYN0TE-024 compared the effectiveness of pembrolizumab monotherapy with a standard platinum combination in patients with advanced NSCLC with a high level of PD-L1 expression without EGFR mutations or ALK translocation. Compared with the platinum doublet the administration of pembrolizumab significantly increased all estimated parameters, including the median of progression-free survival (mPFS was 10.3 months versus 6 months; HR = 0.50; 95% CI 0.37-0.68, p < 0.001), the objective response rate (ORR 44.8% versus 27.8%), duration of response (in the pembrolizumab arm the median was not reached, in the chemotherapy (CT) group - 6.3 months). Despite the approved crossover, the use of pembrolizumab in the 1st line of treatment more than doubled the life expectancy of NSCLC patients with high PD-L1 expression as compared to CT: the median overall survival (OS) was 30.0 months versus 14.2 months (HR = 0.63, p = 0.002), 1-year OS 70.3% versus 54.8%; 2-year OS - 51.5% versus 34.5%. The remaining population to study were untreated patients with any level of PD-L1 expression. A randomized phase 3 study KEYNOTE-189 evaluated the effectiveness of adding pembrolizumab to the platinum combination in the 1st line treatment of non-squamous NSCLC without EGFR and ALK mutations with any PD-L1 expression. The addition of pembrolizumab to the standard 1st line CT significantly increased all estimated efficacy indicators including OS, PFS and ORR. After a median follow-up of 10.5 months the median OS in the pembrolizumab combination group was not reached and in CT group was 11.3 months. The estimated 12-months survival was 69.2% and 49.4% respectively (HR = 0.49; 95% CI 0.38-0,64; p <0.001). The median PFS was 8.8 months versus 4.9 months, alive 1 year without progression 34.1% and 17.3% of patients respectively (HR = 0.52; p <0.001). The ORR in the group with pembrolizumab reached 47.6% versus 18.9% in CT group, moreover the tumor regressions were much longer. Finally a randomized 3-phase study KEYN0TE-407 evaluated the effectiveness of adding pembrolizumab to 1st-line CT of NSCLC with squamous histology with any PD-L1 expression. As the first analysis showed, the addition of permboli-zumab significantly increased OS of patients with squamous NSCLC, median OS 15.9 months versus 11.3 months in the groups of pembrolizumab + CT and placebo + CT respectively (HR = 0.64; 95% CI 0,49-0.95; p = 0.0006), median PFS 6.4 months and 4.8 months respectively (HR = 0.56; 95% CI 0.450.70; p <0, 0001) and OrR 57.9% versus 38.4%, the median response duration 7.7 months versus 4.8 months. Thus, the convincing advantages of using pembrolizumab in 1st line therapy were demonstrated in 3 randomized phase 3 studies: in monotherapy of NSCLC of any histological subtype with high PD-L1 expression, and in combination with CT in squamous and non-squamous hystologies regardless of the level of PD-L1 expression.

scholarly journals Whole Brain Radiotherapy With and Without Concurrent Erlotinib in NSCLC with Brain Metastases: a multicentre, open-label, randomized, controlled phase 3 Trial

2020 ◽  
Author(s):  
Zhenzhou Yang ◽  
Yan Zhang ◽  
Rongqing Li ◽  
Abulimiti Yisikandaer ◽  
Biyong Ren ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Objective Response ◽  
Whole Brain Radiotherapy ◽  
Combination Group ◽  
Open Label ◽  
Phase 3 ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Egfr Mutant ◽  
Nsclc Patients

Abstract Background Erlotinib combined with whole brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase 2 single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase 3, randomized trial. Methods NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n=115) or WBRT combined with erlotinib arms (n=109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by Mini–Mental State Examination (MMSE). Results A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months versus 9.2 months for WBRT-alone (p=0.601). Median PFS and overall survival (OS) of combination group were 5.3 versus 4.0 months (p=0.825) and 12.9 versus 10.0 months (p=0.545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 versus 12.8 months; p=0.164), PFS (8.8 versus 6.4 months; p=0.702) and OS (17.5 versus 16.9 months; p=0.221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments. Conclusion Concurrent erlotinib with WBRT didn’t improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases.

scholarly journals The Impact of Javanica Oil Emulsion Injection on Chemotherapy Efficacy and Cellular Immune Indicators in Patients with Advanced NSCLC: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Huilin Xu ◽  
Zhucheng Yin ◽  
Anbing He ◽  
Dedong Cao
Keyword(s):  
Advanced Nsclc ◽  
Karnofsky Performance Status ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Combination Group ◽  
Control Group ◽  
Oil Emulsion ◽  
Standard Mean Difference ◽  
The Impact

Background. This meta-analysis aimed to evaluate the efficacy and safety of Javanica oil emulsion injection (JOI) combined with chemotherapy versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods. Electronic databases including EMBASE, PUBMED, the Cochrane library, and Chinese Biological Medical disc (CBM) were searched until May 2018. The clinical trials reporting efficacy and immune function of JOI combined with chemotherapy versus chemotherapy in advanced NSCLC were included according to the inclusion and exclusion criteria. Stata 11 and RevMan 5.3 were used for meta-analysis. Results. Twenty-four studies involving 2089 cases were included. The results of the meta-analysis showed that there were significant differences in objective response rate (risk ratio (RR) = 1.17; 95% confidence interval (CI): 1.05–1.29; P<0.05), improvement in Karnofsky Performance Status (standard mean difference (SMD) = 1.59; 95% CI: 1.41–1.77; P<0.01), incidence of adverse events (RR = 0.78; 95% CI: 0.7–0.87; P<0.05), percentage changes of CD3+ cells (SMD = 2.0; 95% CI: 1.49–2.50; P<0.01), CD4+ cells (SMD = 1.55; 95% CI, 1.2–1.9; P<0.01), natural killer cells (SMD = 1.98; 95% CI: 1.15–2.82; P<0.01), but not CD8+ (SMD = −1.44; 95% CI: −4.53–1.65; P=0.36), and value of CD4+/CD8+ (SMD = 0.32; 95% CI: 0.28–0.36; P<0.01) between the JOI combination group and control group. Funnel plot and Begg’s and Egger’s analysis indicated that there was no significant publication bias (P>0.05). Conclusions. JOI may be effective to improve the efficacy of chemotherapy in advanced NSCLC patients, accompanied with better levels of immune cells.

Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer.

1995 ◽  
Vol 13 (12) ◽  
pp. 2879-2885 ◽  
Author(s):  
P M Ravdin ◽  
H A Burris ◽  
G Cook ◽  
P Eisenberg ◽  
M Kane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Response Duration ◽  
Fluid Retention ◽  
Skin Reactions ◽  
Median Response ◽  
High Level

PURPOSE The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone. PATIENTS AND METHODS Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen. RESULTS Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.

CISCA (cisplatin vs. carboplatin) meta-analysis: An individual patient data meta-analysis comparing cisplatin versus carboplatin-based chemotherapy in first-line treatment of advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7011-7011 ◽  
Author(s):  
A. Ardizzoni ◽  
M. Tiseo ◽  
L. Boni ◽  
R. Rosell ◽  
F. V. Fossella ◽  
...  
Keyword(s):  
Randomized Trials ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Objective Response ◽  
Third Generation ◽  
Line Treatment ◽  
First Line ◽  
Risk Of Death ◽  
End Point ◽  
First Line Treatment

7011 Background: The issue of the equivalence between carboplatin and cisplatin in the treatment of advanced NSCLC is still controversial. To answer this question, we conducted an individual patient (pt) data meta-analysis of randomized trials comparing cisplatin- and carboplatin-based chemotherapy (CT) in first-line treatment of advanced NSCLC. Methods: A literature search was performed to identify randomized trials investigating the substitution of carboplatin for cisplatin, combined with the same agent/s, in the first-line CT of advanced NSCLC. The primary end-point was overall survival (OS) and the secondary end-points were response rate (RR) and toxicity. For each end-point the analysis was based on a fixed-effects model. For the study of the effect on OS, Cox proportional hazards model was used. The probability to have an objective response or an adverse event was studied using a logistic regression model. Results: Nine trials were identified and the relative databases obtained. In total, 2,968 pts were randomized to receive CT with cisplatin (1,489) or with carboplatin (1,479), respectively. The RR was 30% and 24% for cisplatin- and carboplatin-based CT, respectively, with an OR of 1.37 (95% C.I.: 1.16–1.62; p < 0.001). Concerning the OS, carboplatin was associated with a relative risk of death 7% higher compared with cisplatin, even if this difference was not statistically significant (HR = 1.07; 95% C.I.: 0.99–1.15; p = 0.101). Patients on cisplatin-based CT had more nausea-vomiting and nephro-toxicity while thrombocytopenia was more frequent during carboplatin-based CT. Subgroup analyses revealed that cisplatin-based CT led to statistically significant advantage in survival in the subgroups of pts with non-squamous tumours and in those treated with third generation CT. Conclusions: CISCA is the first individual pt data meta-analysis on this subject. We found that cisplatin-based is superior to carboplatin-based CT in terms of RR; however, the increased RR does not translate into an OS benefit. Nevertheless, selected pts with advanced NSCLC may obtain slightly more benefit from cisplatin-based third generation CT. No significant financial relationships to disclose.

Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) versus sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4157-TPS4157 ◽  
Author(s):  
Robin Kate Kelley ◽  
Ann-Lii Cheng ◽  
Fadi S. Braiteh ◽  
Joong-Won Park ◽  
Fawzi Benzaghou ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
Disease Etiology ◽  
Multiple Tumor ◽  
First Line Treatment

TPS4157 Background: C inhibits tyrosine kinases involved in tumor growth, angiogenesis, and immune regulation, including MET, VEGFR, and TAM kinases (Tyro3, AXL, MER). C is approved for treatment of aHCC after prior S based on improved overall survival (OS) vs placebo in the phase 3 CELESTIAL trial (Abou-Alfa NEJM 2018). Standard of care for first-line treatment of aHCC is tyrosine kinase inhibition with S or lenvatinib, and phase 3 trials of immune checkpoint inhibitors (ICIs) in first- and second- line aHCC are ongoing. C may promote an immune-permissive tumor environment, which could enhance response to ICIs. C is being evaluated in combination with the anti-PD-L1 antibody A in multiple tumor types including HCC in a phase 1 study; and dose, preliminary clinical activity, and safety have been established in aRCC (Agarwal Ann Oncol 2018). A in combination with bevacizumab, an anti-VEGF antibody, has shown preliminary clinical activity in first-line aHCC (Pishvaian Ann Oncol 2018). Here, we present the study design of a phase 3 trial of C+A vs S in pts with aHCC who have not received prior systemic therapy. Methods: This international, randomized, open-label phase 3 trial (NCT03755791) is evaluating the efficacy and safety of C+A vs S as first-line treatment for aHCC. Eligibility criteria include age ≥18 years, BCLC stage B or C, Child-Pugh A, ECOG PS 0 or 1, and measurable disease per RECIST 1.1. Patients are randomized 6:3:1 to an experimental arm of C (40 mg qd) + A (1200 mg infusion q3w), a control arm of S (400 mg bid), and an exploratory arm of C monotherapy (60 mg qd). 640 pts are planned at ~200 sites globally. Randomization is stratified by disease etiology (HBV [with or without HCV], HCV [without HBV], or other), region (Asia, other), and the presence of extrahepatic disease and/or macrovascular invasion (yes, no). OS and progression-free survival are coprimary endpoints and objective response rate is a secondary endpoint. Additional endpoints include safety, pharmacokinetics, and correlation of biomarker analyses with clinical outcomes. Enrollment in COSMIC-312 is ongoing. Clinical trial information: NCT03755791.

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4666-TPS4666
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Geert-Yan Creemers ◽  
Antonio Cubillo ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .

KRYSTAL-12: A randomized phase 3 study of adagrasib (MRTX849) versus docetaxel in patients (pts) with previously treated non-small-cell lung cancer (NSCLC) with KRASG12C mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9129-TPS9129
Author(s):  
Tony S. K. Mok ◽  
William E. Lawler ◽  
Merrill Kingman Shum ◽  
Shaker R. Dakhil ◽  
Alexander I. Spira ◽  
...  
Keyword(s):  
United States ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
The United States ◽  
Mapk Signaling ◽  
Concurrent Administration ◽  
Phase 3 ◽  
Platinum Based Chemotherapy ◽  
Patient Reported

TPS9129 Background: Despite significant advances in chemotherapy and immunotherapy for advanced NSCLC, the majority of pts ultimately develop progressive disease associated with poor outcomes. KRAS is a key mediator of the RAS/MAPK signaling cascade that promotes cell growth and proliferation. KRASG12C mutations occur in 14% of NSCLC (adenocarcinoma), and mutations in KRAS are associated with a poor prognosis. Although KRAS has historically been undruggable, recent research into the development of agents that specifically bind mutant KRAS has led to the development of direct inhibitors of KRASG12C. Adagrasib, an investigational agent, is a potent, covalent inhibitor of KRASG12C that irreversibly and selectively binds to and locks KRASG12C in its inactive state. Adagrasib was optimized for favorable pharmacokinetic (PK) properties, including oral bioavailability, long half-life (̃24 h), and extensive tissue distribution. Initial results have demonstrated encouraging antitumor activity and tolerability of adagrasib monotherapy in pts with NSCLC harboring a KRASG12C mutation. Methods: KRYSTAL-12 is a multicenter, randomized Phase 3 study evaluating the efficacy of adagrasib (600 mg BID) vs docetaxel in pts with advanced NSCLC harboring a KRASG12C mutation who have progressed during or after treatment with a platinum-based regimen and an immune checkpoint inhibitor. The study is designed to demonstrate improvement in the dual primary endpoints of progression-free survival (PFS) and overall survival (OS). Secondary endpoints include safety, objective response rate (ORR) per RECIST 1.1, duration of response (DOR), plasma PK parameters of adagrasib, and patient-reported outcomes (PROs). The study will also explore correlations between gene alterations (at baseline and upon development of treatment resistance) and efficacy. Approximately 450 patients will be randomized in a 2:1 ratio to receive adagrasib or docetaxel and will be stratified by region (United States/Canada vs other countries) and sequential vs concurrent administration of prior platinum-based chemotherapy and anti–PD-1/PD-L1 antibody. The planned sample size is sufficiently powered for the hypothesized treatment effect of the endpoints. Pts will receive study treatment until disease progression, unacceptable adverse events, investigator decision to terminate treatment, or patient withdrawal. This study is currently enrolling and will be open at sites in the United States, Europe, and Asia. Clinical trial information: NCT04685135.

Assessment of sacituzumab govitecan (SG) in patients with prior neoadjuvant/adjuvant chemotherapy in the phase 3 ASCENT study in metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1080-1080
Author(s):  
Lisa A. Carey ◽  
Delphine Loirat ◽  
Kevin Punie ◽  
Aditya Bardia ◽  
Veronique Dieras ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Clinical Benefit ◽  
Objective Response ◽  
Phase 3 ◽  
Median Response ◽  
Aggressive Disease ◽  
Metastatic Setting ◽  
Neo Adjuvant Chemotherapy ◽  
Line Of Therapy

1080 Background: mTNBC is a heterogenous disease with few treatment options and poor outcomes. Pts who recur ≤ 12 mo after completing (neo)adjuvant chemotherapy may represent a subset with more aggressive disease. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated approval for pts with mTNBC who received ≥ 2 prior therapies for metastatic disease; clinical benefit for SG over treatment of physician's choice (TPC) was confirmed in the phase 3 ASCENT study (NCT02574455) for median progression-free survival (PFS; 5.6 vs 1.7 mo), median overall survival (OS; 12.1 vs 6.7 mo), objective response rate (ORR; 35% vs 5%), clinical benefit rate (CBR; 45% vs 9%), and median duration of response (6.3 vs 3.6 mo). This ASCENT subanalysis of pts with mTNBC who recurred ≤ 12 mo after (neo)adjuvant chemotherapy and then only received 1 line of therapy in the metastatic setting assessed the benefit of SG in this subgroup vs the overall trial population. Methods: In ASCENT, pts with mTNBC refractory/relapsing after ≥ 2 prior chemotherapies were randomized 1:1 to receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine). Per protocol, a pt was eligible after only 1 prior regimen in the metastatic setting if their disease recurred within 12 months of completing (neo)adjuvant therapy. Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Efficacy and safety was assessed in a subset of pts who recurred ≤ 12 mo after (neo)adjuvant chemotherapy and then received 1 line of therapy in the metastatic setting. Results: In total, 33 and 32 BMNeg pts with a median age of 49 and 51 yrs received SG and TPC in this subgroup, respectively. In this subgroup, treatment with SG (vs TPC) improved PFS (median 5.7 vs 1.5 mo; HR, 0.41; 95% CI, 0.22-0.76; P = 0.0049) and OS (median 10.9 vs 4.9 mo; HR, 0.51; 95% CI, 0.28-0.91; P = 0.0227). We also observed higher ORR (30% vs 3%) and CBR (42% vs 6%) with a median response duration of 6.7 mo with SG vs not calculable with TPC. The efficacy results from this subgroup are similar to those for SG vs TPC in the overall BMNeg population. The safety profile of SG in pts in this subgroup was consistent with prior reports. There were no treatment-related deaths with SG. Conclusions: Pts with mTNBC who recurred ≤ 12 mo after (neo)adjuvant therapy and then had 1 line of prior therapy in the metastatic setting may represent a subset with more aggressive disease. In this subgroup, pts had superior outcomes with SG vs TPC in the second-line metastatic setting, consistent with the benefit seen in the overall BMNeg population. Studies are ongoing (NeoSTAR, NCT04230109; SASCIA, NCT04595565) to evaluate SG as an earlier-line treatment option for TNBC. Clinical trial information: NCT02574455 .

The efficacy and safety profile of anlotinib plus docetaxel as second-line treatment in advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21068-e21068
Author(s):  
Zhiqiao Xu ◽  
Yan Zhang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Small Cell Lung

e21068 Background: Docetaxel is a standard second line treatment in advanced NSCLC, but the treatment effect is limited. Previous studies, such as REVEL, demonstrated that anti angiogenic therapy combined with docetaxel had significantly therapeutic efficacy. Anlotinib is an oral multi target angiogenesis TKI targeting the VEGFR, FGFR, PDGFR and c Kit. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC, and this study aims to investigate the efficacy and safety of Anlotinib combined with docetaxel in second-line treatment in advanced non-small cell lung cancer (NSCLC). Methods: This is a single-center, single-arm clinical trial. A group of 30 patients of histologically or cytologically confirmed, locally advanced stage IIIB-IV NSCLC and with ECOG PS 0-1 were admitted to the Kaifeng Central Hospital Cancer Center. Patients who progressed after first-line treatment were treated with anlotinib (12 mg p.o., QD d1 to 14, q3w) combined with docetaxel (75mg/m2, iv, QD, d1 to 14, q3w) as the second-line therapy. The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 30 patients were enrolled from October 2018 to April 2020. At data cutoff (Sept. 30, 2020), 30 patients were available for efficacy analysis. The median progression-free survival (mPFS) was 7.5 months (2.0-18.5). Among these patients, there was 1 CR, 9 PR, 15 SD, 5 PD, resulting in the ORR = 33.33% and the DCR = 83.33%. The Cox multivariate analysis showed that stage is an independent risk factor affecting prognosis ( p= 0.003). The most common grade 3 AEs were leukopenia (23,3%), neutropenia (13.3%), hypertension (13.3%), which can be controlled, and no grade 4 or grade 5 AEs occurred. Conclusions: Second line anlotinib plus docetaxel showed clinical benefit in advanced NSCLC patients in terms of PFS, ORR and DCR, and the incidence of adverse reactions are tolerable. This combination might be a promising option for patients advanced NSCLC.

A single-arm phase Ib study of multiple target cytotoxic T-lymphocyte (MCTL) in combination with toripalimab as second-line therapy in advanced non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2535-2535
Author(s):  
Xiubao Ren ◽  
Weihong Zhang
Keyword(s):  
T Lymphocyte ◽  
Advanced Nsclc ◽  
Cytotoxic T Lymphocyte ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
Multiple Target ◽  
Open Label ◽  
Open Label Phase ◽  
Ecog Ps

2535 Background: Anti-PD-1/ PD-L1 (programmed cell-death 1) mAb treatment has been approved in the US and in Europe as second-line treatment for advanced NSCLC because of the good tolerance and efficacy in comparison with docetaxel. Unfortunately, The objective response rate is only around 20%. Multiple Target Cytotoxic T-lymphocyte (MCTL) cells can restore the antitumor immunity to improve patient outcome. Combining MCTL cells with anti-PD-1 mAb may strengthen the results as second-line treatment in patients with advanced NSCLC. (NCT04193098). Methods: This is a single-center, open-label, phase 1b trial of combination MCTL cells with toripalimab (anti-PD-1 mAb)as second-line treatment for advanced NSCLC. Systemic therapy patients received toripalimab every 3 weeks for 12 cycles and received MCTL cells every 3 weeks for 9 cycles, then toripalimab and MCTL cells for maintenance therapy until disease progression or unacceptable toxicity. Results: From June 2019 to October 2020, 14 pts aged 43-70 years (median age 59 years) were enrolled. The squamous/non-squamous ratio was 50%/50%. 8 (57.1%) were men, 13(92.8%) were ECOG PS=0-1, 5 (35.7%) had pleural effusion, and 3 (21.4%) had bone metastases. Among 13 evaluable pts, the ORR and DCR were 38.4% and 71.4%, At the time of data cutoff, the median DOR was not reached (range 8.25m-NA), the median PFS was 399 days (range 192d-NA), and the median OS were not mature. Adverse events (AEs) occurred in 5 (38.4%), No grade≥3 AEs events occurred. Immune-related AEs were thyroid hypofunction (3, 23%) and weak (2, 15.4%). Biomarkers which correlated with efficacy and AEs are being analyzed. Conclusions: Multiple Target Cytotoxic T-lymphocyte (MCTL) in combination with toripalimab as second-line treatment for advanced NSCLC because of the well tolerated and encouraging efficacy. Further studies are warranted to confirm these results. Research Sponsor: Tianjin Medical University Cancer Institute and Hospital. Clinical trial information: NCT04193098.

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