Overall survival benefit of Osimertinib and clinical value of upfront cranial local therapy in untreated EGFR ‐mutant non‐small cell lung cancer with brain metastasis

2021 ◽  
Author(s):  
Yang Zhao ◽  
Shuyan Li ◽  
Xi Yang ◽  
Li Chu ◽  
Shengping Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Survival Benefit ◽  
Local Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Value ◽  
Overall Survival Benefit ◽  
Egfr Mutant

Statewide rates of adjuvant checkpoint inhibitor use after definitive chemoradiation for stage III non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8523-8523
Author(s):  
Alex K. Bryant ◽  
Huiying Yin ◽  
Matthew J. Schipper ◽  
Peter Alexander Paximadis ◽  
Thomas Pence Boike ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Benefit ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Definitive Chemoradiation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Overall Survival Benefit

8523 Background: In the landmark PACIFIC trial, adjuvant durvalumab after definitive chemoradiation for unresectable stage III non-small-cell lung cancer (NSCLC) produced a 11% absolute overall survival benefit at two years compared to placebo, and the US Food and Drug Administration approved durvalumab for this indication in February 2018. We investigated the real-world use of adjuvant durvalumab and other immune checkpoint inhibitors (ICI) in a contemporary cohort of patients. Methods: We identified patients with unresectable stage III (AJCC 8th edition) NSCLC treated with definitive chemoradiation from February 2018 to March 2020 from a statewide radiation oncology quality consortium, representing a mix of community (n=22 centers, 336 patients) and academic practice settings (n=5 centers, 64 patients) across the state of Michigan. Use of adjuvant durvalumab or other ICI (atezolizumab, nivolumab, or pembrolizumab) was ascertained at the time of routine three- or six-month follow-up after completion of chemoradiation. Baseline characteristics of patients treated with or without adjuvant ICI were compared with the Chi-squared test for categorical variables and a two-sided t-test for continuous variables. Results: Of 400 patients with unresectable stage III NSCLC treated with definitive chemoradiation, 268 (67%) received adjuvant ICI. Of these, the majority received durvalumab (86%) followed by pembrolizumab (7.5%) and nivolumab (6.0%). The proportion of patients receiving ICI remained stable throughout the study period with no discernable time trends. Eight-five percent of white patients received ICI compared with 77% of black patients (p=0.04), but there were no differences in gender (54.5% male in ICI vs 52.3% no ICI), current smoking (42.2% ICI vs 37.9% no ICI, p=0.68), number of comorbidities (29.5% with 3 or more comorbidities in ICI vs. 26.5% in no ICI, p=0.86), baseline oxygen use (8.9% ICI vs 10.6% no ICI, p=0.59), age (median 66.4 years [IQR 60.3-73.4] for ICI vs. 66.9 years [IQR 61.1-72.2] no ICI, p=0.89), treatment at an academic center (16.0% ICI vs 15.9% no ICI, p=0.97), or ECOG performance status (59.3% ECOG 0 in ICI vs 62.8% no ICI). Conclusions: In a broad range of academic and community-based practices across a state including 27 sites, only two-thirds of potentially eligible stage III NSCLC patients received adjuvant durvalumab or other ICI agents despite a proven overall survival benefit. Receipt of ICI was not strongly associated with baseline demographic or comorbidity variables. Further work will seek to clarify the patient-level reasons behind non-initiation of adjuvant ICI.

Vandetanib Versus Placebo in Patients With Advanced Non–Small-Cell Lung Cancer After Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor: A Randomized, Double-Blind Phase III Trial (ZEPHYR)

2012 ◽  
Vol 30 (10) ◽  
pp. 1114-1121 ◽  
Author(s):  
Jin Soo Lee ◽  
Vera Hirsh ◽  
Keunchil Park ◽  
Shukui Qin ◽  
Cesar R. Blajman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Survival Benefit ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Overall Survival Benefit

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor (EGFR), and RET signaling. This placebo-controlled trial assessed whether vandetanib conferred an overall survival benefit in patients with advanced non–small-cell lung cancer (NSCLC) after prior treatment with an EGFR tyrosine kinase inhibitor and one or two chemotherapy regimens. Patients and Methods Eligible patients were randomly assigned 2:1 to receive vandetanib 300 mg/d or placebo until disease progression or unacceptable toxicity. The primary objective was to compare the outcomes between the two arms with respect to overall survival. Results Overall, 924 patients received vandetanib (n = 617) or placebo (n = 307). No significant increase in overall survival was detected in the vandetanib cohort compared with placebo (hazard ratio = 0.95; 95.2% CI, 0.81 to 1.11; P = .527); median overall survival was 8.5 months versus 7.8 months for vandetanib and placebo patients, respectively. Statistically significant advantages favoring vandetanib were observed for progression-free survival (hazard ratio = 0.63; P < .001) and objective response rate (2.6% v 0.7%; P = .028). Postprogression therapy was balanced across the cohorts in both number and type. Adverse events were generally consistent with previous NSCLC studies of vandetanib 300 mg; common events occurring with a greater frequency in the vandetanib arm versus placebo included diarrhea (46% v 11%), rash (42% v 11%), and hypertension (26% v 3%). Conclusion The study did not demonstrate an overall survival benefit for vandetanib versus placebo. There was a higher incidence of some adverse events with vandetanib.

scholarly journals EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis

2019 ◽  
Vol 18 ◽  
pp. 32-38 ◽  
Author(s):  
Devarati Mitra ◽  
Yu-Hui Chen ◽  
Richard Li ◽  
Gretchen Hermann ◽  
Katelyn Atkins ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Increased Risk ◽  
Egfr Mutant

scholarly journals SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer

2019 ◽  
Vol 37 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Nathan A. Pennell ◽  
Joel W. Neal ◽  
Jamie E. Chaft ◽  
Christopher G. Azzoli ◽  
Pasi A. Jänne ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Phase Ii Trial ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stage Ia ◽  
Epidermal Growth ◽  
Egfr Mutant

Purpose Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non–small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC. Materials and Methods In this open-label phase II trial, patients with resected stage IA to IIIA (7th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%. Results Patients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months. Conclusion Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.

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