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Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations.

Zwitter M, Stanic K, Rajer M, Kern I, Vrankar M, Edelbaher N, Kovac V - Radiol Oncol (2014)

Bottom Line: Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15.After 4 to 6 cycles, patients continued with erlotinib maintenance.PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Oncology Ljubljana, Ljubljana, Slovenia ; Faculty of Medicine, University of Maribor, Maribor, Slovenia.

ABSTRACT

Background: Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).

Patients and methods: Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.

Results: Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2-3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.

Conclusions: While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.

No MeSH data available.


Related in: MedlinePlus

Progression-free and overall survival of treated patients (n = 53).Progression-free survival for epidermal growth-factor receptor (EGFR) wild-type patients (median 6.0 months, 95% confidence interval [CI] 3.9 – 8.1) and for patients with EGFR activating mutations (median 21.2 months, 95% CI 15.3 – 27.1)Overall survival for EGFR wild-type patients (median 7.6 months, 95% CI 5.0 – 10.2) and for patients with EGFR activating mutations (median 32.5 months, 95% CI 21.2 – 43.7)
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f2-rado-48-04-361: Progression-free and overall survival of treated patients (n = 53).Progression-free survival for epidermal growth-factor receptor (EGFR) wild-type patients (median 6.0 months, 95% confidence interval [CI] 3.9 – 8.1) and for patients with EGFR activating mutations (median 21.2 months, 95% CI 15.3 – 27.1)Overall survival for EGFR wild-type patients (median 7.6 months, 95% CI 5.0 – 10.2) and for patients with EGFR activating mutations (median 32.5 months, 95% CI 21.2 – 43.7)

Mentions: Median PFS for all EGFR mutant patients was 21.2 months (95% CI 15.3 – 27.1 months) (Figure 2). No significant difference in PFS was seen when comparing patients with exon 19 deletions to those with other mutations (data not shown).


Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations.

Zwitter M, Stanic K, Rajer M, Kern I, Vrankar M, Edelbaher N, Kovac V - Radiol Oncol (2014)

Progression-free and overall survival of treated patients (n = 53).Progression-free survival for epidermal growth-factor receptor (EGFR) wild-type patients (median 6.0 months, 95% confidence interval [CI] 3.9 – 8.1) and for patients with EGFR activating mutations (median 21.2 months, 95% CI 15.3 – 27.1)Overall survival for EGFR wild-type patients (median 7.6 months, 95% CI 5.0 – 10.2) and for patients with EGFR activating mutations (median 32.5 months, 95% CI 21.2 – 43.7)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230556&req=5

f2-rado-48-04-361: Progression-free and overall survival of treated patients (n = 53).Progression-free survival for epidermal growth-factor receptor (EGFR) wild-type patients (median 6.0 months, 95% confidence interval [CI] 3.9 – 8.1) and for patients with EGFR activating mutations (median 21.2 months, 95% CI 15.3 – 27.1)Overall survival for EGFR wild-type patients (median 7.6 months, 95% CI 5.0 – 10.2) and for patients with EGFR activating mutations (median 32.5 months, 95% CI 21.2 – 43.7)
Mentions: Median PFS for all EGFR mutant patients was 21.2 months (95% CI 15.3 – 27.1 months) (Figure 2). No significant difference in PFS was seen when comparing patients with exon 19 deletions to those with other mutations (data not shown).

Bottom Line: Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15.After 4 to 6 cycles, patients continued with erlotinib maintenance.PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Oncology Ljubljana, Ljubljana, Slovenia ; Faculty of Medicine, University of Maribor, Maribor, Slovenia.

ABSTRACT

Background: Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).

Patients and methods: Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.

Results: Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2-3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.

Conclusions: While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.

No MeSH data available.


Related in: MedlinePlus