scholarly journals Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC

2019 ◽  
Vol 14 (10) ◽  
pp. 1794-1806 ◽  
Author(s):  
Scott J. Antonia ◽  
Ani Balmanoukian ◽  
Julie Brahmer ◽  
Sai-Hong I. Ou ◽  
Matthew D. Hellmann ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Clinical Activity ◽  
Long Term Follow Up

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

Modern Treatment of Non-Small Cell Lung Cancer with Intracerebral Metastases and Extracranial Metastatic Affection of Liver, Mediastinal Lymph Nodes, Skeletal Bones. Clinical Observation

2021 ◽  
Vol 66 (3) ◽  
pp. 82-87
Author(s):  
Yu. Udalov ◽  
A. Samoylov ◽  
L. Danilova ◽  
E. Slobina ◽  
E. Stepanyuchenko ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Mediastinal Lymph Nodes ◽  
Small Cell Lung ◽  
Antitumor Therapy ◽  
Modern Methods ◽  
Long Term Follow Up

Introduction: The article covers issues related to modern methods of treatment of non-small cell lung cancer (NSCLC) with multiple synchronous metastases in brain, liver, mediastinal lymph nodes, skeletal bones and describes a clinical case of modern effective treatment and long-term follow-up of a patient with advanced NSCLC and extra- and intracranial metastatic spread. Purpose: Evaluation of modern methods of special antitumor treatment and their application in clinical practice for the treatment of metastatic NSCLC. Material and methods: Modern methods of proton and photon radiation therapy, targeted therapy are considered. Results: The use of modern methods of special antitumor therapy has increased the overall and relapse-free survival rate of patients with multiple metastases of NSCLC in brain, liver, mediastinal lymph nodes, skeletal bones reducing the need for additional interventions. This is confirmed by a long-term follow-up after modern effective antitumor treatment of a patient with advanced NSCLC and synchronous progression in the form of extra- and intracranial metastatic spread. The patient has been alive for more than 2 years from the moment of progression with an estimated life expectancy of 4–5 months. Conclusion: Modern methods of special antitumor therapy can increase the survival rate of patients with multiple synchronous NSCLC metastases in brain, liver, mediastinal lymph nodes, skeletal bones without significant deterioration in their quality of life.

Randomized trial of thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer (NSCLC): Long-term follow-up of Japan Clinical Oncology Group (JCOG) Study JCOG0301.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8532-8532 ◽  
Author(s):  
Shinji Atagi ◽  
Junki Mizusawa ◽  
Satoshi Ishikura ◽  
Toshiaki Takahashi ◽  
Hiroaki Okamoto ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Late Toxicity ◽  
Initial Report ◽  
Locally Advanced Nsclc ◽  
Long Term Follow Up ◽  
Grade 3

8532 Background: In the phase III JCOG0301 trial, concurrent chemoradiotherapy (CRT) was compared with radiotherapy (RT), demonstrating clinically significant survival benefits in elderly patients with locally advanced NSCLC after a median follow-up of 19.4 months. However, the long-term patterns and cumulative incidences of toxicity associated with CRT and RT are poorly understood for elderly patients. We report long-term survival data and late toxicities after a minimum follow-up of 6.4 years. Methods: Eligible patients were older than 70 years and had unresectable stage III NSCLC. They were randomly assigned to RT alone (RT arm: irradiation with 60 Gy in 30 fractions) or CRT (CRT arm: the same RT with additional concurrent use of carboplatin 30 mg/m2 per fraction up to the first 20 fractions). The primary endpoint was overall survival (OS). Prognosis and adverse events data were collected beyond those in the initial report of this trial. Kaplan-Meier survival curves and 3- and 5-year survival proportions were calculated. Late toxicities were defined as occurring later than 90 days after RT initiation. Results: From September 2003 to May 2010, 200 patients (RT arm, n = 100; CRT arm, n = 100) were enrolled. Consistent with the initial report, the CRT arm had better OS than the RT arm (HR = 0.743, 95% CI = 0.552 – 0.998, one-sided p = 0.0239 by stratified log-rank test). In the RT and CRT arms, median OS was 16.5 and 21.7 months, 3-year survival was 16.3% and 34.3%, and 5-year survival was 9.2% and 15.2%, respectively. %Grade 3/4 late toxicities were 7.4% (heart 2.1%, lung 5.3%) in the RT arm (n = 94) and 7.5% (esophagus 1.1%, lung 6.5%) in the CRT arm (n = 93). No additional cases of late toxicity (Grade 3/4) were seen since the initial report. There were 7 treatment-related deaths, all of which were recorded in the initial report: 4 (4.0%) in the RT arm and 3 (3.0%) in the CRT arm. Conclusions: Long-term follow-up confirms the survival benefits of CRT for elderly patients with locally advanced NSCLC. There was no observed increase in late toxicity with CRT, as compared with RT alone. Clinical trial information: 00132665.

scholarly journals Long-Term Follow-Up Results of Postoperative Radiotherapy in 36 Patients with Acromegaly

2000 ◽  
Vol 85 (7) ◽  
pp. 2476-2482 ◽  
Author(s):  
Nienke R. Biermasz ◽  
Hans van Dulken ◽  
Ferdinand Roelfsema
Keyword(s):  
Serum Insulin ◽  
Effective Intervention ◽  
Clinical Activity ◽  
Oral Glucose ◽  
Pituitary Hormone ◽  
Age Related ◽  
Igf I ◽  
Long Term Follow Up

In acromegaly, pituitary irradiation is a slow, but effective, intervention in decreasing GH concentration. Few studies addressing the outcome of radiotherapy have used the currently accepted strict criteria for remission in the analysis of data. These studies report a low percentage of remission after radiotherapy. Doubt has especially been raised as to whether radiotherapy is effective in normalizing serum insulin-like growth factor (IGF)-I concentration. We analyzed the long-term follow-up data of postoperatively administered radiotherapy in 36 patients with postoperative persistent acromegaly, using both the normalization of GH suppression during oral glucose loading (GTT) and the normalization of IGF-I concentration as criteria for remission. Before radiotherapy, mean suppressed GH was 9.8 ± 1.9 mU/L (n = 31), and mean IGF-I concentration was 44.3 ± 3.9 nmol/L, equivalent to + 4.76 ± 0.78 age-related IGF-I sd score (n = 13). The median radiation dose was 40 Gray (range, 25–50 Gray). At 5, 10, and 15 yr follow-up, 18 out of 30 patients (60%), 23 out of 31 patients (74%), and 16 out of 19 patients (84%), respectively, achieved normal serum IGF-I concentration. At the last assessment of all patients, after a mean follow-up period of 139 ± 12 months, 27 out of 36 (75%) patients had a normal IGF-I concentration without additional medication, whereas 5 patients still required treatment with octreotide. Remission, as judged by normalization of GH suppression during GTT, was documented in 65% of patients from 2–5 yr after radiotherapy (n = 34); in 69% of patients, up to 10 yr after radiotherapy (n = 29); and in 71% of patients, up to 15 yr post irradiation (n = 17). At the latest assessment, a mean of 125± 11 months after radiotherapy, 71% of patients (n = 35) were in remission, as defined by normal suppression of serum GH during GTT. Remission, as judged by normalization of both GTT and IGF-I, was found in 40% of patients 3–5 yr after radiotherapy (n = 30); in 61% of patients, 6–10 yr after radiotherapy (n = 28); in 65%, after 11–15 yr after radiotherapy (n = 17); and in 63% of patients, at the end of the follow-up period (n = 35). Substitution of one or more pituitary hormone deficiencies was required in 11% of patients postoperatively; in 29%, 5 yr after radiotherapy; in 54%, 10 yr after radiotherapy; and in 58%, more than 15 yr after radiotherapy. Our findings support the use of radiotherapy as an effective intervention in the treatment of residual clinical activity of disease after surgery for acromegaly.

EARLY PREDICTION OF LONG-TERM RESPONSE TO NATALIZUMAB IN MULTIPLE SCLEROSIS

2015 ◽  
Vol 86 (11) ◽  
pp. e4.22-e4
Author(s):  
Joel Raffel ◽  
Arie Gafson ◽  
Samer Dahdaleh ◽  
Richard Nicholas
Keyword(s):  
Multiple Sclerosis ◽  
Post Treatment ◽  
Clinical Activity ◽  
First Year ◽  
Disability Progression ◽  
Long Term Follow Up ◽  
Observational Cohort ◽  
Term Response

IntroductionIn people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict poor prognosis. However, this association has not been studied in those receiving natalizumab.MethodologyData were collected on early relapses and new MRI activity from an observational cohort of 161 patients on natalizumab, with long-term follow-up. Two outcome measures were used. The first – ‘Clinical Activity Years 1–3’ – defined non-responders as those with relapses or EDSS progression at years 1–3 post-treatment, versus baseline. The second – ‘Disability Progression Years 3+’ – defined non-responders as those with EDSS progression at 3–7 years post-treatment, versus baseline.Results‘Clinical Activity Years 1–3’ was strongly predicted by early relapses (Odds Ratio (OR) 8.4, p<0.0001), and by a combined score of early relapses and MRI activity (Modified Rio Score 1: OR 4.9, p<0.001. Modified Rio Score 2: OR 19.0, P<0.01). In contrast, ‘Disability Progression Years 3+’ was not predicted by early relapses or MRI activity.ConclusionsRelapses and new MRI activity within the first year of starting natalizumab predict short-term outcomes, but not long-term disability outcomes. This requires further validation in other cohorts.

Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapy-refractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4014-4014 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Patrick Alexander Ott ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Clinical Activity ◽  
Heavily Pretreated ◽  
Long Term Follow Up ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

4014 Background: In the phase 3 ONO-12 study, 3rd- or later-line nivolumab (N) monotherapy prolonged OS vs placebo in Asian pts with adv G/GEJ cancer (median OS, 5.3 vs 4.1 mo; HR, 0.63; P < 0.0001; ASCO-GI 2017, Kang YK et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). The phase 1/2 CheckMate 032 study showed favorable clinical activity of N ± ipilimumab (I) in Western pts with adv CTx-R G/E/GEJ cancer (NCT01928394). We report updated long-term follow-up data of G/E/GEJ pts in CheckMate 032. Methods: Pts received N 3 mg/kg Q2W (N3), N 1 mg/kg + I 3 mg/kg Q3W (N1+I3), or N 3 mg/kg + I 1 mg/kg Q3W (N3+I1). Primary endpoint was ORR. Secondary endpoints included DOR, OS, PFS, and safety. Efficacy in pts by PD-L1 status was assessed. Results: 160 heavily pretreated pts (79% had ≥ 2 prior Tx) were enrolled (N3, n = 59; N1+I3, n = 49; N3+I1, n = 52); 24% had PD-L1+ (≥ 1%) tumors. ORR was 12% in N3, 24% in N1+I3, and 8% in N3+I1. In pts with PD-L1 ≥ 1%, ORR was 19% (3/16) in N3, 40% (4/10) in N1+I3, and 23% (3/13) in N3+I1; in pts with PD-L1 < 1%, ORR was 12% (3/26), 22% (7/32), and 0% (0/30), respectively. Median DOR was 7.1 mo in N3, 7.9 mo in N1+I3, and NA in N3+I1. OS in all pts and in pts with PD-L1 ≥ 1% is in the Table. Grade 3–4 treatment-related AEs reported in ≥ 10% of pts in any treatment arm were diarrhea (N3, 2%; N1+I3, 14%; N3+I1, 2%), ALT increased (N3, 3%; N1+I3, 14%; N3+I1, 4%), and AST increased (N3, 5%; N1+I3, 10%; N3+I1, 2%). Conclusions: N ± I led to durable responses and long-term OS in heavily pretreated Western pts with adv G/E/GEJ cancer, which is consistent with the clinical activity observed in Asian pts in the ONO-12 study. Safety was consistent with prior reports. These data support ongoing investigation of N ± I in pts with adv G/E/GEJ cancer. Clinical trial information: NCT01928394. [Table: see text]

Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

2019 ◽  
Vol 42 ◽  
Author(s):  
John P. A. Ioannidis
Keyword(s):  
Mental Health ◽  
Mental Disease ◽  
Brain Disorders ◽  
Social Stressors ◽  
Labor Education ◽  
Mental Diseases ◽  
Long Term Follow Up ◽  
Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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