Randomized phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma: CALGB 30406.

Wang, X. F.; Socinski, Mark A.; Crawford, J.; Capelletti, Marzia; Edelman, Martin J.; Villalona‐Calero, Miguel A.; Kratzke, Robert A.; Vokes, Everett E.; Miller, V. A.

doi:10.1200/jco.2010.28.15_suppl.7503

Cited by 53 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prospective trials have shown response rates of approximately 75% in patients with EGFR mutations (in exons 19 and 21) who are treated with erlotinib or gefitinib (4)(5)(6)(7). In patients with EGFR mutations, singleagent erlotinib and erlotinib with chemotherapy have similar efficacy, but single-agent erlotinib is less toxic (8). Gefitinib showed a progression-free survival (PFS) advantage over chemotherapy as a first-line therapy in 3 randomized phase III trials in patients with EGFR mutant lung adenocarcinoma (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib

Janjigian

Azzoli

Krug

et al. 2011

Clinical Cancer Research

108

View full text Add to dashboard Cite

Purpose: In patients with epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma, treatment with erlotinib or gefitinib is associated with a 75% radiographic response rate and progressionfree survival of approximately 12 months. The most common mechanism of acquired resistance to erlotinib is development of a secondary mutation in EGFR, suggesting that these tumors continue to depend on EGFR signaling. We hypothesized that combined EGFR blockade would overcome acquired resistance to erlotinib in patients with lung adenocarcinoma. To evaluate the toxicity and efficacy of cetuximab and erlotinib in patients with acquired resistance to erlotinib, we conducted this phase I/II clinical trial.Experimental Design: Patients with lung adenocarcinoma and clinically defined acquired resistance to erlotinib were treated with erlotinib 100 mg daily, along with cetuximab every 2 weeks in three escalating dose cohorts (250 mg/m 2 , 375 mg/m 2 , and 500 mg/m 2 ). The recommended phase II dose was then evaluated in a two-stage trial, with a primary end point of objective response rate.Results: A total of 19 patients were enrolled. The most common toxicities for the combination of cetuximab and erlotinib were rash, fatigue, and hypomagnesemia. The recommended phase II dose identified was cetuximab 500 mg/m 2 every 2 weeks and erlotinib 100 mg daily. At this dose and schedule, no radiographic responses were seen (0 of 13, 0%, 95% CI, 0-25).

show abstract

Section: Introductionmentioning

confidence: 99%

Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib

Janjigian

Azzoli

Krug

et al. 2011

Clinical Cancer Research

108

View full text Add to dashboard Cite

show abstract

“…Two Japanese studies have shown gefitinib to be more effective than platinum/taxane doublet chemotherapy as first-line treatment for patients with NSCLC harboring EGFR mutations; significant improvements in progression-free survival (PFS) were observed for gefitinib compared with both carboplatin/paclitaxel (PFS 10.8 versus 5.4 months; HR: 0.3; 95% CI 0.22 to 0.41; p < 0.001) [Maemondo et al 2010] and cisplatin/docetaxel (PFS 9.2 versus 6.3 months; HR: 0.49; 95% CI 0.34 to 0.71; p < 0.001) [Mitsudomi et al 2010]. The CALGB 30406 study is investigating the efficacy of the EGFR TKI erlotinib administered alone and in combination with carboplatin/paclitaxel in never/former light smokers with chemotherapy-naïve, advanced NSCLC, and has reported a significantly increased PFS for patients with EGFR mutations compared with wild-type EGFR [Janne et al 2010]. Interestingly, in this study erlotinib monotherapy had similar efficacy to combination therapy in EGFR-mutated tumors.…”

Section: Introductionmentioning

confidence: 99%

The potential for crizotinib in non-small cell lung cancer: a perspective review

Bang

2011

Ther Adv Med Oncol

View full text Add to dashboard Cite

Tyrosine kinases have a crucial role as key regulators of signaling pathways that influence cell differentiation and growth. Dysregulation of tyrosine kinase-mediated signaling is understood to be an important oncogenic driver. Genetic rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) gene occur in non-small cell lung cancer (NSCLC), anaplastic large cell lymphomoas, inflammatory myofibroblastic tumors, and other cancers. Cells with abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib. This review will highlight the discovery of the fusion between echinoderm microtubuleassociated protein-like 4 (EML4) and ALK as an oncogenic driver, recognition of other ALK gene rearrangements in NSCLC, and the confirmation that crizotinib is an effective treatment for patients with ALK-positive NSCLC. Work is underway to further define the role for crizotinib in the treatment of ALK-positive lung cancer and other cancers and to investigate the molecular mechanisms for resistance to ALK inhibition with crizotinib.

show abstract

“…This was the first trial to demonstrate an improvement in response rate and 12-month progression-free rate in patients with EGFR mutation-positive NSCLC treated with an EGFR TKI compared to chemotherapy (71.2 vs. 47.1 % and 25 vs. 7 %, hazard ratio (HR) for progression or death 0.74, respectively). Several trials comparing gefitinib and erlotinib to chemotherapy in EGFR mutation-positive NSCLC patients have demonstrated similar results with progression-free survival (PFS) ranging from 9.2 to 13.1 months and no significant improvement in OS; the lack of benefit in OS is thought to be due to high rates of crossover to the EGFR TKI after progression with chemotherapy [10][11][12][13][14].…”

Section: First-generation Egfr Inhibitorsmentioning

confidence: 89%

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress

Castellanos

Horn

2015

Curr. Treat. Options in Oncol.

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) mutations have been detected in approximately 10 % of North American patients diagnosed with non-small cell lung cancer (NSCLC). Approximately 90 % of these mutations are exon 19 deletions or exon 21 L858R point mutations. First- and second-generation EGFR tyrosine kinase inhibitors (TKIs) are approved as first-line therapy based on clinical trials demonstrating superior response rates, progression free survival (PFS), and overall survival (OS) compared to chemotherapy in patients with EGFR mutation-positive NSCLC treated with an EGFR TKI prior to chemotherapy. However, the majority of patients treated with an EGFR TKI develop resistance to therapy within about 12 months, approximately 50 % of patients due to a second site mutation, the T790M mutation occurring within exon 20. At the time of progression, the EGFR TKI is most commonly discontinued and a different systemic therapy is initiated. However, oncogene addiction persists and recent exciting data with third-generation EGFR TKIs suggests that acquired resistance may be surmountable. The newest EGFR TKIs have shown activity against EGFR-mutant NSCLC after progression on first-generation TKIs, including those with T90M, while sparing wild-type EGFR and hence appear to be both well tolerated and efficacious. At this time, it appears that third-generation EGFR TKIs are effective following first-generation therapy, and determining the most appropriate sequence to maximize overall survival is a matter of ongoing investigation. As the arsenal of active agents in EGFR mutant NSCLC grows, future research into potential combinations, optimal timing, and resistance mechanisms of these new treatments, as well as their possible role in the adjuvant, post-chemoradiation, and neoadjuvant settings holds great promise for this group of patients.

show abstract

Randomized phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma: CALGB 30406.

Cited by 53 publications

References 0 publications

Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib

Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib

The potential for crizotinib in non-small cell lung cancer: a perspective review

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress

Contact Info

Product

Resources

About