An FDA analysis of the association of tumor growth rate and overall and progression-free survival in metastatic non-small cell lung cancer (NSCLC) patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9541-9541
Author(s):  
Yutao Gong ◽  
Jeremy Mason ◽  
Yuan-Li Shen ◽  
Elaine Chang ◽  
Dickran Kazandjian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Rate ◽  
Clinical Trials ◽  
Progression Free Survival ◽  
Small Cell ◽  
Tumor Growth Rate ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumor Measurements ◽  
Line Of Therapy

9541 Background: Previous studies have suggested that tumor growth rate (g), estimated using prostate-specific antigen values, is associated with overall survival (OS) in prostate cancer (Wilkerson, 2016). We performed a retrospective pooled analysis in non-small cell lung cancer (NSCLC) to investigate the extent to which g values estimated using radiological tumor measurements in clinical trials are associated with survival. Methods: We identified 24 randomized clinical trials submitted to FDA between 2013 and 2019 investigating either immune checkpoint inhibitor (ICI) or targeted therapy (TT) in pts with metastatic NSCLC. Of 9934 patients (pts) enrolled, 5532 pts (2401, 1189, and 1942 pts treated with ICI, TT, and chemotherapy respectively) had sufficient data to derive a valid g. The g was evaluated by both type and line of therapy. Pts were then grouped according to quartiles of g, with Q1 being the lowest. We calculated OS and progression-free survival (PFS) for each group via the Kaplan-Meier method, and used the Cox model for group comparison. Results: Median g was 9.7E-4, 1.4E-3, and 2.2E-3/day, and median OS was 34.2, 21.3, and 15.3 months (mo), in pts treated with TT, ICI, and chemotherapy, respectively, regardless of lines of therapy. When treated with the same type of therapy, pts receiving 2nd line therapy had a higher median g than those receiving 1st line. The median survival and log-rank hazard ratios for pts treated with 1st line ICI monotherapy are shown in the Table. Conclusions: TT is associated with the lowest median g, followed by ICI, and then chemotherapy, perhaps due to patient selection, better inherent biology/natural history, or favorable results of TT on selected tumors. Regardless, we found that g is inversely associated with survival, across treatment types. This relationship is also observed in pts treated with the same type and line of therapy (for example, 1st line ICI), where Q1 has the longest survival, followed by Q2, Q3, and then Q4. In summary, our exploratory analysis suggests that g derived from radiological tumor measurements in NSCLC may relate to survival. Prospective studies are needed to evaluate if g might be an earlier endpoint compared to classical response criteria. [Table: see text]

Erlotinib for Advanced Non–Small-Cell Lung Cancer in the Elderly: An Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21

2008 ◽  
Vol 26 (14) ◽  
pp. 2350-2357 ◽  
Author(s):  
Paul Wheatley-Price ◽  
Keyue Ding ◽  
Lesley Seymour ◽  
Gary M. Clark ◽  
Frances A. Shepherd
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Elderly Patients ◽  
National Cancer Institute ◽  
Age Groups ◽  
Young Patients ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

PurposeNational Cancer Institute of Canada Clinical Trials Group Study BR.21 established erlotinib as a standard of care in patients with non–small-cell lung cancer (NSCLC) after failure of first- or second-line chemotherapy. The current study analyzes the influence of age on outcomes in BR.21.Patients and MethodsBR.21 was a double-blind phase III trial that randomly assigned 731 patients to erlotinib 150 mg daily or placebo. End points included progression-free survival and overall survival (OS), response, quality of life (QOL), drug exposure, and toxicity, which are analyzed in this retrospective study by the following two age groups: ≥ 70 years (elderly) or less than 70 years (young).ResultsThere were 163 elderly patients (112 on erlotinib, 51 on placebo) and 568 young patients (376 on erlotinib, 192 on placebo). There was no significant difference between age groups randomly assigned to erlotinib or placebo in progression-free survival (elderly: 3.0 v 2.1 months; hazard ratio [HR] = 0.63; 95% CI, 0.44 to 0.90; P = .009; young: 2.1 v 1.8 months; HR = 0.64; 95% CI, 0.53 to 0.76; P < .0001; interaction, P = .77) or OS (elderly: 7.6 v 5.0 months; HR = 0.92; 95% CI, 0.64 to 1.34; P = .67; young: 6.4 v 4.7 months; HR = 0.73; 95% CI, 0.61 to 0.89; P = .0014; interaction, P = .31). Response rates were similar between age groups. Elderly patients, compared with young patients, had significantly more overall and severe (grade 3 and 4) toxicity (35% v 18%; P < .001), were more likely to discontinue treatment as a result of treatment-related toxicity (12% v 3%; P < .0001), and had lower relative dose-intensity (64% v 82% received > 90% planned dose; P < .001).ConclusionElderly patients treated with erlotinib gain similar survival and QOL benefits as younger patients but experience greater toxicity.

Prognostic value of peripheral naive CD8+ T cells in oligometastatic non-small-cell lung cancer

2021 ◽  
Author(s):  
Xin Zhao ◽  
Yan Zhang ◽  
Zhenlin Gao ◽  
Yaguang Han
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

A phase II study of anlotinib plus whole brain radiation therapy (WBRT) for advanced non-small cell lung cancer with multiple brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21063-e21063
Author(s):  
Xiangzhi Zhu ◽  
Hua Tao ◽  
Ming Jiang ◽  
Meiqi Shi ◽  
Cheng Kong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Brain Metastases ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Multiple Brain Metastases ◽  
Common Grade

e21063 Background: The prognosis of non-small-cell lung cancer (NSCLC) patients(pts) with multiple brain metastases is poor. WBRT is the main treatment for the pts, but QUARTZ study showed that the efficacy of WBRT is unsatisfactory. The synergistic effect of the antiangiogenic therapy with radiation therapy has been well established. Anlotinib, an antiangiogenic multi-target TKI, had significantly improved progression-free survival (PFS) of advanced NSCLC with Brain Metastases. This study aimed to evaluate the efficacy and safety of anlotinib combined with WBRT in pts with brain metastases ( > 3) from advanced NSCLC. Methods: Advanced NSCLC pts with brain metastases ( > 3) who were histologically confirmed to be driver gene wild type or positive and pts who had received two or more previous treatments were eligible. Pts with meningeal metastasis were excluded. All pts were treated with anlotinib (12 mg, QD, day 1 to 14 of a 21-day cycle) combined with WBRT (DT 30Gy/12f), followed by maintenance therapy with anlotinib until disease progression or treatment intolerance. The primary endpoint was intracranial progression-free survival (iPFS). Secondary endpoints were extracranial PFS (ePFS), OS and toxicity. Results: As of 25 Jan 2021, 28 pts were enrolled. The median age was 57.5 years with 46.4% male. 89.3% of pts with adenocarcinoma. 21.4% pts harbored EGFR mutation. A total of 25 pts were included in efficacy analysis. In intracranial evaluation, ORR was 64.0%, DCR was 88.0%, median iPFS was 11.1 months (95% CI 5.9 to 12.1). In extracranial evaluation, ORR was 12.0%, DCR was 84.0%, median ePFS was 6.0months (95% CI 3.2 to 8.8). Most common grade 1-2 adverse events (AEs) were hypertension (67.8%), fatigue (64.2%)，anorexia (46.4%) and hand and foot skin reaction (37.5%). The most common grade 3-4 AEs were hypertension (12.5%), hand and foot skin reaction (10.7%) and fatigue (7.2%). No intracranial hemorrhage occurred during treatment. Dose adjustment due to AE occurred in 21.4% patients. Conclusions: This prospective study shows that the combination of anlotinib and WBRT for patients with multiple brain metastases after standard treatment resistance exhibited an effective therapeutic approach and manageable AEs. For further investigation, large sample and additional clinical trials are warranted. Clinical trial information: ChiCTR1900022093.

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