Twenty-Two Years of Phase III Trials for Patients With Advanced Non–Small-Cell Lung Cancer: Sobering Results

Breathnach, Oscar S.; Freidlin, Boris; Conley, Barbara A.; Green, Mark R.; Johnson, David H.; Gandara, David R.; O’Connell, Michael J.; Shepherd, Frances A.; Johnson, Bruce E.

doi:10.1200/jco.2001.19.6.1734

Cited by 322 publications

(184 citation statements)

References 35 publications

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“…Our results were consistent with those from a previous IPD-based analysis of ECOG trials, which reported improved survival in more recent NSCLC trials. 10 Breathnach et al, who investigated the changes in trial characteristics and outcomes of 33 Phase III trials that were initiated from 1973 to 1994 in North America, reported an improvement in survival over time (P ¼ .0214), with an increase of approximately 0.1 month per year, 9 which also was consistent with our study results. Thus, the outcomes of patients with advanced NSCLC from around the world who were enrolled in Phase III trials, along with the outcomes of patients entered on trials that were conducted in North America, seem to have improved consistently over the years.…”

Section: Discussionsupporting

confidence: 91%

“…Breathnach et al also noted that platinum-based therapy was associated independently with survival prolongation (P ¼ .0318). 9 Wakelee et al observed a significant survival advantage from cisplatin in their patients with NSCLC (hazard ratio, 0.882; P < .0001). 10 In addition, we observed a significant survival benefit from cisplatin-based regimens compared with noncisplatin-containing regimens irrespective of the year of trial initiation (an increase of 0.9631 months [28.89 days] with cisplatin; P < .0001) ( Table 3).…”

Section: Discussionmentioning

confidence: 96%

“…9,10 To avoid publication bias, both published and unpublished trials were identified through a computer-based search of the PubMed database and abstracts from the 10 past conferences of the American Society of Clinical Oncology. We conducted the search by using the following search terms: lung neoplasm, carcinoma, nonsmall cell, chemotherapy, and randomized controlled trial.…”

Section: Search For Trialsmentioning

confidence: 99%

“…Their results indicated that patient survival improved with the passage of time. 9 However, the majority of the trials that were included in their analysis were investigations of older chemotherapeutic regimens, and they included scarcely any trials that investigated the efficacy of newer developed agents or molecular-targeted agents. Thus, the more recent trends in outcomes from clinical trials for patients with advanced NSCLC remain unclear.…”

mentioning

confidence: 99%

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Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first‐line, systemic chemotherapy

Hotta¹,

Fujiwara²,

Matsuo³

et al. 2007

Cancer

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BACKGROUND.Few studies have assessed formally whether treatment outcomes have improved substantially over the years for patients with advanced nonsmall cell lung cancer (NSCLC) enrolled in Phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials.METHODS.The literature was searched to identify trials that addressed the role of chemotherapy regimens in the first‐line setting for the treatment of advanced NSCLC. Trends were tested by using multiple regression analysis.RESULTS.In total, 121 Phase III trials were identified that involved 42,768 patients with 263 chemotherapy arms and 11 best supportive care (BSC) arms, all of which were initiated between 1982 and 2002. Although the number of randomized patients and the proportion of patients with metastatic disease had increased over the years, the number of patients with a poor performance status who were accrued into the trials had decreased. Cisplatin‐based chemotherapy was been investigated most frequently during the period. The multiple regression analysis revealed a significant improvement in median survival and in the median time to disease progression over the years, with annual prolongations of 0.1203 months (3.609 days) and 0.0617 months (1.851 days), respectively (P< .0001 and P < .0130, respectively). In addition, the use of cisplatin and carboplatin was associated significantly with survival prolongation. The median survival for patients who received BSC also increased progressively over the years (P = .0487).CONCLUSIONS.The survival of patients with NSCLC in Phase III trials improved slowly but steadily over time, although the main factors responsible for this improvement remain unknown. Nonetheless, the current results also suggested that novel targets and new agents will be required in the future fight against advanced NSCLC. Cancer 2007 © 2007 American Cancer Society.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Section: Search For Trialsmentioning

confidence: 99%

mentioning

confidence: 99%

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Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first‐line, systemic chemotherapy

Hotta¹,

Fujiwara²,

Matsuo³

et al. 2007

Cancer

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“…The initial therapy for advanced non-small-cell lung cancer (NSCLC) is systemic chemotherapy with a two-drug combination regimen, which often includes a platinum agent, but the median survival of patients treated with such regimens has ranged from only 8 to 10 months. Little improvement in the efficacy of chemotherapy has been made in the last 20 years (Breathnach et al, 2001;Kelly et al, 2001;Schiller et al, 2002).…”

mentioning

confidence: 99%

EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib

et al. 2006

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Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumour response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC). Pleural effusion is a common complication of lung cancer. In this study, we assessed the feasibility of detection of EGFR mutations in samples of pleural effusion fluid. We obtained 43 samples, which was the cell-free supernatant of pleural fluid, from Japanese NSCLC patients, and examined them for EGFR mutations. The epidermal growth factor receptor mutation status was determined by a direct sequencing method (exons 18 -21 in EGFR). EGFR mutations were detected in 11 cases (E746_A750del in seven cases, E746_T751del insA in one case, L747_T751del in one case, and L858R in two cases). The EGFR mutations were observed more frequently in women and non-smokers. A comparison between the EGFR mutant status and the response to gefitinib in the 27 patients who received gefitinib revealed that all seven patients with partial response and one of the seven patients with stable disease had an EGFR mutation. No EGFR mutations were detected in the patients with progressive disease. The results suggest that DNA in pleural effusion fluid can be used to detect EGFR mutations and that the EGFR mutation status may be useful as a predictor of the response to gefitinib.

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Benefits of Adding a Drug to a Single-Agent or a 2-Agent Chemotherapy Regimen in Advanced Non–Small-Cell Lung Cancer

Delbaldo

Michiels

Syz³

et al. 2004

JAMA

322

169

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Twenty-Two Years of Phase III Trials for Patients With Advanced Non–Small-Cell Lung Cancer: Sobering Results

Cited by 322 publications

References 35 publications

Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first‐line, systemic chemotherapy

Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first‐line, systemic chemotherapy

EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib

Benefits of Adding a Drug to a Single-Agent or a 2-Agent Chemotherapy Regimen in Advanced Non–Small-Cell Lung Cancer

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