Chemotherapy for advanced non-small cell lung cancer patients with performance status 2

Blackhall, Fiona; Bhosle, Jaishree; Thatcher, Nicholas

doi:10.1097/01.cco.0000152629.20996.9e

Cited by 21 publications

(10 citation statements)

References 28 publications

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“…However, the monthly chest radiographs would trigger a CT scan before the protocol timelines, and overall survival was the primary trial endpoint. Also, we included patients of performance status 2, for whom, on the basis of evidence reported in 2005, 15 chemotherapy could improve survival, and a phase 2 study 16 has shown that doublet chemotherapy has a better survival than single agent chemotherapy. However, when TOPICAL was designed, provision of chemotherapy to such patients was not routine practice because many studies with second and third generation chemotherapy had not shown survival benefit, and many of these patients had serious adverse events 17,18 .…”

Section: Discussionmentioning

confidence: 99%

First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial

Lee¹,

Khan²,

Upadhyay³

et al. 2012

The Lancet Oncology

162

123

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SummaryBackgroundMany patients with advanced non-small-cell lung cancer (NSCLC) receive only active supportive care because of poor performance status or presence of several comorbidities. We investigated whether erlotinib improves clinical outcome in these patients.MethodsTOPICAL was a double-blind, randomised, placebo-controlled, phase 3 trial, done at 78 centres in the UK. Eligibility criteria were newly diagnosed, pathologically confirmed NSCLC; stage IIIb or IV; chemotherapy naive; no symptomatic brain metastases; deemed unsuitable for chemotherapy because of poor (≥2) Eastern Cooperative Oncology Group performance status or presence of several comorbidities, or both; and estimated life expectancy of at least 8 weeks. Patients were randomly assigned (by phone call, in a 1:1 ratio, stratified by disease stage, performance status, smoking history, and centre, block size 10) to receive oral placebo or erlotinib (150 mg per day) until disease progression or unacceptable toxicity. Investigators, clinicians, and patients were masked to assignment. The primary endpoint was overall survival. Analyses were by intention to treat, and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment. This study is registered, number ISRCTN 77383050.FindingsBetween April 14, 2005, and April 1, 2009, we randomly assigned 350 patients to receive erlotinib and 320 to receive placebo. We followed up patients until March 31, 2011. 657 patients died; median overall survival did not differ between groups (erlotinib, 3·7 months, 95% CI 3·2–4·2, vs placebo, 3·6 months, 3·2–3·9; unadjusted hazard ratio [HR] 0·94, 95% CI 0·81–1·10, p=0·46). 59% (178 of 302) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash, which was the only independent factor associated with overall survival. Patients with first-cycle rash had better overall survival (HR 0·76, 95% CI 0·63–0·92, p=0·0058), compared with placebo. Compared with placebo, overall survival seemed to be worse in the group that did not develop first-cycle rash (1·30, 1·05–1·61, p=0·017). Grade 3 or 4 diarrhoea was more common with erlotinib than placebo (8% [28 of 334] vs 1% [four of 313], p=0·0001), as was high-grade rash (23% [79 of 334] vs 2% [five of 313], p<0·0001); other adverse events were much the same between groups.InterpretationPatients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib. Patients who develop a first-cycle rash should continue to receive erlotinib, whereas those who do not have a rash after 28 days should discontinue erlotinib, because of the possibility of decreased survival.FundingCancer Research UK, Roche.

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Section: Discussionmentioning

confidence: 99%

First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial

Lee¹,

Khan²,

Upadhyay³

et al. 2012

The Lancet Oncology

162

123

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“…PS 2 patients constitute at least 35–40% of newly diagnosed patients with advanced NSCLC and have a markedly shorter survival compared to good PS patients. (4) They experience enhanced adverse effects with systemic therapies and as a consequence have to a great extent been excluded from clinical trials. Available information on treatment outcomes in this population are confined to a limited number of prospective trials and retrospective subset analyses from several phase III trials.…”

Section: Introductionmentioning

confidence: 99%

“…Available information on treatment outcomes in this population are confined to a limited number of prospective trials and retrospective subset analyses from several phase III trials. (4–7)…”

Section: Introductionmentioning

confidence: 99%

Southwest Oncology Group Phase II Trial (S0341) of Erlotinib (OSI-774) in Patients with Advanced Non-small Cell Lung Cancer and a Performance Status of 2

Hesketh

Chansky

Hirsch

et al. 2008

Journal of Thoracic Oncology

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Purpose This phase II study (S0341) evaluated the efficacy and tolerability of single-agent erlotinib in unselected chemotherapy-naïve patients with advanced non-small cell lung cancer (NSCLC) and a performance status (PS) of 2. Exploratory analyses of a number of biomarkers relating to EGFR pathway activation were also performed. Patients and Methods Patients with stage IIIB (pleural effusion) or stage IV NSCLC with a PS of 2 and no prior chemotherapy or biologic treatment for NSCLC received erlotinib 150 mg daily. Results A total of 81 patients entered the study; 76 were assessable. One complete and 5 partial responses were noted for an overall response rate of 8% (95% CI 3%–16%).Stable disease (SD) was seen in 26 patients (34 %) resulting in a disease control rate (DCR=CR/PR/SD) of 42%. Progression free and median survival were 2.1 months (95% CI 1.5–3.1) and 5 months (95% CI 3.6–7.2) respectively. One-year survival was 24% (95% CI 15%–34%). Although treatment was generally well tolerated, grade 3–4 toxicity was reported in 30 patients (40%), including fatigue (16%), rash (9%), diarrhea (7%) and anorexia (7%). There was one possible treatment related death (pneumonitis). Conclusion In chemotherapy-naïve patients with advanced NSCLC and a PS of 2, single agent erlotinib resulted in an acceptable but significant level of treatment-related side effects. With an overall DCR of 42% and median survival of 5 months, results are comparable to those achieved with chemotherapy in this population. Development of an EGFR-directed biomarker selection strategy may optimize use of erlotinib in PS 2 patients.

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“…Although chemotherapy is a standard treatment for NSCLC with response rates of 30% to 40%, NSCLC patients eventually develop resistance to chemotherapy agents resulting in a median survival of only 8 to 10 months [2]. Recently substantial development in molecular targeted therapy is necessary approach in addition to chemotherapy to treat NSCLC because molecular targeted therapy drugs can interfere with and block specific molecular pathways that regulate critical cancer cell growth, survival and progression, such as EGFR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs expression profile of gefitinib resistant non-small cell lung cancer HCC827 cells

Quan¹,

Seong²

2016

V J Bio

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Chemotherapy for advanced non-small cell lung cancer patients with performance status 2

Cited by 21 publications

References 28 publications

First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial

First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial

Southwest Oncology Group Phase II Trial (S0341) of Erlotinib (OSI-774) in Patients with Advanced Non-small Cell Lung Cancer and a Performance Status of 2

MicroRNAs expression profile of gefitinib resistant non-small cell lung cancer HCC827 cells

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