KEYNOTE-001: 3-year overall survival for patients with advanced NSCLC treated with pembrolizumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9011-9011 ◽  
Author(s):  
Natasha B. Leighl ◽  
Matthew David Hellmann ◽  
Rina Hui ◽  
Enric Carcereny Costa ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Safety Data ◽  
Current Data ◽  
Smoking History ◽  
First Line ◽  
Term Survival ◽  
Previously Treated ◽  
Nsclc Patients

9011 Background: Pembrolizumab (pembro) is approved as first-line (1L) treatment for advanced NSCLC patients (pts) with PD-L1 tumor proportion score (TPS) ≥50% and as treatment for previously treated advanced NSCLC pts with PD-L1 TPS ≥1%. Here we present 3-y OS results for pts enrolled in KEYNOTE-001 (NCT01295827), the first trial evaluating pembro in advanced NSCLC pts. Methods: 550 pts received pembro 2 or 10 mg/kg Q3W or 10 mg/kg Q2W until intolerable toxicity, progression, or investigator or pt decision to withdraw. PD-L1 expression was assessed by IHC using the 22C3 antibody. Survival was assessed every 2 mo after treatment discontinuation. Results: 550 advanced NSCLC pts enrolled; 101 were first line (1L), and 449 were previously treated. As of the Sept 1, 2016, data cutoff, median follow-up duration was 34.5 mo (range, 25.7-51.5 mo); 8 (7.9%) 1L pts and 28 (6.2%) previously treated pts were still on treatment. 3-y OS was 26.4% (95% CI, 14.3%-40.1%) in 1L pts and 19% (95% CI, 15.0%-23.4%) in previously treated pts. 3-y OS rate and median OS by PD-L1 status are in the Table. Additional description of the pts with long-term survival, including updated safety data as well as 3-y OS by smoking history, histology, EGFRstatus, and prior radiation therapy, will be presented. Conclusions: Pembro provides promising long-term OS benefit for 1L and previously treated advanced NSCLC pts expressing PD-L1. The current data represent the longest efficacy and safety follow-up for pts with advanced NSCLC treated with pembro. Clinical trial information: NCT01295827. [Table: see text]

scholarly journals Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Life Expectancy ◽  
Cost Effective ◽  
Base Case ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

scholarly journals Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up

2018 ◽  
Vol 36 (33) ◽  
pp. 3315-3323 ◽  
Author(s):  
Sandra Lockmer ◽  
Bjørn Østenstad ◽  
Hans Hagberg ◽  
Harald Holte ◽  
Ann-Sofie Johansson ◽  
...  
Keyword(s):  
Optimal Timing ◽  
Indolent Lymphoma ◽  
First Line ◽  
Term Outcome ◽  
Cross Sectional ◽  
Term Survival ◽  
Long Term Outcome ◽  
New Therapy

Purpose For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. Methods Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations. Results At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%. Conclusion Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.

scholarly journals A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

2019 ◽  
Vol 23 (3) ◽  
pp. 510-519 ◽  
Author(s):  
Li-Tzong Chen ◽  
Taroh Satoh ◽  
Min-Hee Ryu ◽  
Yee Chao ◽  
Ken Kato ◽  
...  
Keyword(s):  
Placebo Group ◽  
Gastroesophageal Junction ◽  
Phase 3 ◽  
Double Blind ◽  
Term Survival ◽  
Gastroesophageal Junction Cancer ◽  
Programmed Death ◽  
Previously Treated

Abstract Background Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein. Methods ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min–max) follow-up period was 27.3 (24.1–36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status. Results Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60–6.37] vs 4.14 [3.42–4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51–0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65—not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified. Conclusions Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.

Randomized trial of amifostine in locally advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and hyperfractionated radiation (HRT): Long-term survival results of Radiation Therapy Oncology Group (RTOG) 9801

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7529-7529
Author(s):  
B. Movsas ◽  
J. Moughan ◽  
C. Langer ◽  
M. Werner-Wasik ◽  
N. Nicolaou ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Radiation Therapy Oncology Group ◽  
Disease Free Survival ◽  
Rank Test ◽  
Term Survival ◽  
Long Term Survival ◽  
Patient Reported ◽  
Nsclc Patients

7529 Purpose: This analysis was conducted to address the potential antitumor effect of amifostine (AM) in NSCLC patients enrolled on RTOG-9801. The long-term survival results of RTOG-9801 are presented here. Methods: 243 patients (pts) with stage II/IIIAB NSCLC received induction paclitaxel (P) 225 mg/m2IV days 1, 22 and carboplatin (C) AUC 6 days 1, 22 and then concurrent weekly P (50 mg/m2) and C (AUC 2) and HRT (69.6 Gy at 1.2 Gy BID). Pts were randomly assigned to AM 500 mg IV 4x/week or no-AM during chemoradiation. Treatment differences for overall and disease-free survival (OS & DFS) were analyzed with the log-rank test; Gray's test was used for time to progression (TTP). Results: 118 pts were randomly assigned to receive AM and 121 to no-AM (4 pts were ineligible). The median follow-up for pts still alive is 52.3 months (mo) for the AM-arm and 58.3 mo for the no-AM arm (16.6 vs 17.9 for all pts). There are no significant differences in OS, DFS or TTP between arms. The median survival, 3-yr, and 5-yr OS are 17.1 mo, 27% and 17% (AM-arm) vs 18.4 mo, 28% and 16% (no-AM arm) (p=0.97). Grade 3/4/5 late-RT toxicities are similar (11%/3%/2% AM-arm vs 14%/4%/2% no-AM arm). Conclusion: While an earlier publication reported that amifostine did not reduce objective measures of severe esophagitis in RTOG-9801, patient-reported outcome analyses suggested a possible advantage to AM with decreased pain and swallowing symptoms (J Clin Oncol 23:2145–2154, 2005). This long-term follow-up analysis on survival shows no evidence of tumor radioprotection due to amifostine. The promising 5-yr OS suggests that induction paclitaxel/carboplatin (P/C) followed by concurrent RT and weekly low-dose P/C is comparable to other regimens using cisplatin doublets at higher dosages every 3–4 weeks. Research supported by NCI and Medimmune Oncology. No significant financial relationships to disclose.

Estimating long-term survival of PD-L1-expressing, previously treated, non-small cell lung cancer patients who received pembrolizumab in KEYNOTE-001 and -010.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 77-77 ◽  
Author(s):  
Matthew David Hellmann ◽  
Junshui Ma ◽  
Edward B. Garon ◽  
Rina Hui ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Survival Rate ◽  
Survival Models ◽  
Small Cell Lung ◽  
Stat Assoc ◽  
Term Survival ◽  
Long Term Survival ◽  
Previously Treated ◽  
Term Benefit

77 Background: Pembrolizumab showed promising activity in patients with advanced non–small cell lung cancer (NSCLC) in the KEYNOTE-001 study (NCT01295827) and significantly prolonged overall survival (OS) compared with docetaxel in the randomized KEYNOTE-010 study (NCT01905657). Responses to pembrolizumab appear to be remarkably durable, making long-term survival possible in some patients. Typical parametric survival models do not account for the possibility of long-term survival. An alternative, well-established class of statistical models called long-term survival models can be used to directly estimate the percentage of patients achieving long-term survival (>5 years), called “long-term survival rate.” (Berkson J, Gage RP. J Am Stat Assoc. 1952;47:501-515.)(Tsodikov AD et al. J Am Stat Assoc. 2003;98:1063-1078.) Methods: Data from patients with PD-L1–expressing (tumor proportion score ≥1%), previously treated, advanced NSCLC in KEYNOTE-001 and KEYNOTE-010 were used. KEYNOTE-001 data were used to initially estimate the long-term survival rate of pembrolizumab, while KEYNOTE-010 data were used for subsequent independent validation. Point estimates of long-term survival rates with their 95% CIs based on the model described above are reported. Results: Based on the long-term survival model, the estimated long-term survival rate in pembrolizumab-treated population in KEYNOTE-001 (n = 306) is 25.4% (95% CI, 15.2%-33.3%) and the intention-to-treat population who received pembrolizumab in KEYNOTE-010 (n = 690) is 25.3% (95% CI, 8.9%-36.9%). In contrast, the long-term survival rate of docetaxel arm (n = 343) in KEYNOTE-010 is estimated to be 3.2% (95% CI, 0%-17.4%). Conclusions: In 2 independent data sets, it is estimated that 25% of patients with previously treated PD-L1–expressing NSCLC may achieve long-term benefit from pembrolizumab monotherapy. Long-term survival models can provide an early estimate of long-term benefit from pembrolizumab using data with limited follow-up time. Long-term follow-up from these trials will further validate this finding. MDH and JM are co-first authors.

Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA9015-LBA9015 ◽  
Author(s):  
Edward B. Garon ◽  
Matthew David Hellmann ◽  
Enric Carcereny Costa ◽  
Natasha B. Leighl ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Locally Advanced ◽  
Metastatic Nsclc ◽  
Immune Mediated ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Phase 1B ◽  
Clinical Trial Information

LBA9015 Background: Pembrolizumab (pembro) monotherapy has demonstrated durable antitumor activity in advanced PD-L1–expressing NSCLC. We present 5-y OS for patients (pts) enrolled in the phase 1b KEYNOTE-001 study (NCT01295827), the first trial evaluating pembro in advanced NSCLC. These data provide the longest efficacy/safety follow-up for NSCLC pts treated with pembro. Methods: Pts had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by IHC using the 22C3 antibody. Pts received pembro 2 mg/kg Q3W or 10 mg/kg Q2W or Q3W. The primary efficacy endpoint was ORR. OS was a secondary endpoint. Results: 550 pts were enrolled (treatment-naive, n=101; previously treated, n=449). As of November 5, 2018 (data cutoff), median (range) follow-up was 60.6 (51.8–77.9) mo; 82% (n=450/550) had died. Estimated 5-y OS rates were 23.2% for treatment-naive pts and 15.5% for previously treated pts (Table). ORR (by investigator per irRC) was 42% (95% CI, 32–52) for treatment-naive pts and 23% (95% CI, 19–27) for previously treated pts. Median (range) DOR was 16.8 (2.1+ to 55.7+) mo and 38.9 (1.0+ to 71.8+) mo, respectively. Immune-mediated AEs had occurred in 17% of pts at 5 y, similar to the incidence reported at 3-y follow-up. Additional results, including outcomes in key subgroups and detailed safety follow-up data, will be presented. Conclusions: In KEYNOTE-001, 5-y OS rate was 23.2% in treatment-naive pts and 15.5% in previously treated pts with advanced NSCLC treated with pembro, compared to a historical rate of ~5% (per SEER 2008–2014), prior to the introduction of anti–PD-1 therapy. 5-y OS rate was at least 25% in pts with PD-L1 TPS ≥50% in both pt populations in KEYNOTE-001. Clinical trial information: NCT01295827. [Table: see text]

Efficacy of EGFR-TKIs monotherapy versus TKI plus chemotherapy as first-line treatment in EGFR mutant lung adenocarcinoma with liver metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21099-e21099
Author(s):  
Huijuan Wang ◽  
Mengmeng Li ◽  
Mina Zhang ◽  
Zhang guo Wei ◽  
Xiangtao Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liver Metastases ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Small Cell Lung ◽  
First Line ◽  
Chemotherapy Group ◽  
Nsclc Patients ◽  
Egfr Tkis

e21099 Background: Liver metastasis is one of the most reasons for the poor prognosis of patients with advanced lung cancer. Seeking for active and effective treatment measures is very important for these patients. At present, the first-line standard treatment of the advanced NSCLC with EGFR mutation is EGFR-TKIs monotherapy. However, its efficacy is poor in the advanced non-small cell lung cancer with EGFR mutation and liver metastases. The objective of this study is to evaluate the efficacy of EGFR-TKIs plus chemotherapy in patients with EGFR mutation of advanced non-small cell lung cancer with liver metastases. Methods: The clinical data of a total of 384 advanced NSCLC patients with EGFR mutation positive who were admitted to The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital from February 2017 to June 2020 were retrospectively analyzed. There were 75 patients with liver metastases. Patients were divided into two groups, and accepted EGFR-TKIs monotherapy or EGFR-TKIs plus chemotherapy, respectively. All patients treatment response were evaluated by the RECIST1.1 Response evaluation criteria in solid tumors.Progression free-survival (PFS) were also analyzed. Results: In the study, 75 patients were finally screened. There were 37 patients in the EGFR-TKIs monotherapy group and 38 patients in the TKI plus chemotherapy group. The median follow-up time was 23.0 months. At the latest follow-up date (2021-01-01), 57 patients had disease progression and 35 patients had died. Comparing with EGFR-TKIs monotherapy,the first-line PFS of EGFR-TKI plus chemotherapy group was longer, and the median PFS was 12.7 months VS 7.4 months (P = 0.018).The ORR of primary lung lesions was no significant difference between these two groups（65.8%VS 51.4% P = 0.204), and DCR (97.4% VS 94.6% P = 0.981) also had no difference between two groups（P > 0.05）. ORR of liver metastases in the EGFR-TKIs plus chemotherapy group was significantly higher than EGFR-TKIs monotherapy group ORR (65.8%VS 40.5%，P = 0.028). Conclusions: In advanced NSCLC patients with EGFR mutation and liver metastases, comparing with EGFR-TKIs monotherapy, taking EGFR-TKIs plus chemotherapy as first-line treatment had longer PFS, and better efficacy on liver lesions.

scholarly journals PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4583
Author(s):  
María Rosario García Campelo ◽  
Edurne Arriola ◽  
Begoña Campos Balea ◽  
Marta López-Brea ◽  
José Fuentes-Pradera ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Meta Analysis ◽  
Safety Data ◽  
Phase Iii ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Significant Difference ◽  
Safety Outcomes ◽  
Using Data ◽  
Nsclc Patients

This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667–0.783, p = 0.002), and grade 3–5 AEs (RR = 0.406 95% CI: 0.340–0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29–0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs.

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