Three Cases of Long-Lasting Tumor Control with Erlotinib after Progression with Gefitinib in Advanced Non-Small Cell Lung Cancer

Gridelli, Cesare; Maione, Paolo; Galetta, Domenico; Colantuoni, G.; Gaizo, Filomena Del; Ferrara, Carmine; Guerriero, Ciro; Nicolella, Dario; Rossi, Antonio

doi:10.1097/jto.0b013e3180cc25b0

Cited by 31 publications

(16 citation statements)

References 16 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several retrospective studies have described the clinical activity of one EGFR-TKI treatment after the failure of another [18,19,20,21,22,23,24] or readministration of the same drug [14,15,25]. Most such reports have noted favorable results, although Viswanathan et al [19 ]and Costa et al [24 ]reported no or only a limited response to erlotinib after progression on gefitinib.…”

Section: Discussionmentioning

confidence: 92%

Phase II Study of Gefitinib Readministration in Patients with Advanced Non-Small Cell Lung Cancer and Previous Response to Gefitinib

Asahina

Oizumi

Inoue³

et al. 2010

Oncology

View full text Add to dashboard Cite

Objective: Salvage treatment for acquired resistance to gefitinib has yet to be developed. We conducted the first prospective phase II study of gefitinib readministration in previous gefitinib responders. Methods: Gefitinib (250 mg/day) was readministered to patients with advanced/metastatic non-small cell lung cancer who had achieved objective response to initial gefitinib and subsequently received cytotoxic chemotherapy after disease progression with initial gefitinib. The primary endpoint was the objective response rate with gefitinib readministration. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), quality of life, and toxicity. Changes in lung cancer-related symptoms were evaluated using the seven-item lung cancer subscale of the questionnaire. Results: Sixteen patients were enrolled between February 2005 and January 2008. Most had received ≧3 regimens of chemotherapy. Response and disease-control rates for all patients were 0 and 44%. Median PFS and OS were 2.5 and 14.7 months, respectively. Four of 7 patients with stable disease experienced a long duration (≧6 months) of disease control without severe toxicity. Symptom improvement was observed in 2 of 12 patients (17%) for whom quality of life was evaluable. Conclusion: Gefitinib represents a useful therapeutic option for selected previous gefitinib responders.

show abstract

Section: Discussionmentioning

confidence: 92%

Phase II Study of Gefitinib Readministration in Patients with Advanced Non-Small Cell Lung Cancer and Previous Response to Gefitinib

Asahina

Oizumi

Inoue³

et al. 2010

Oncology

View full text Add to dashboard Cite

show abstract

“…Tumor regression in the brain was observed in chemonaive patients as well as in relapse after previous gefitinib treatment and also in patients who were previously judged resistant to gefitinib and who were intermittently treated with chemotherapy. In addition, erlotinib has been successfully applied in patients with previous progression under gefitinib [17,18] but also the inverse sequence has been used with success [18]. One of the most exciting developments is the application of lapatinib, a dual tyrosine kinase inhibitor against both Her2=neu and EGFR in patients with breast cancers metastatic to the brain.…”

Section: Targeting Egfr and Her2=neu In Patients With Brain Metastasismentioning

confidence: 98%

Experimental treatment of brain metastases

Greil

2008

memo

View full text Add to dashboard Cite

The rapid development of targeted therapies capable of entering the brain and the emerging technology of nano shells armed with cytotoxins reflects promising progress in the treatment of brain metastasis. The management of brain metastases is complicated by a number of major problems. The histological, molecular, biologic and immunologic nature of the various tumour types metastasizing to the brain differs significantly. As a consequence, the sensitivity towards various cytotoxic drugs or other treatment options varies substantially. Only few drugs are usually considered capable of penetrating the blood=brain and the brain=liquor barriers. Thus, the availability of a drug with adequate molecular size and pharmacokinetics within the compartments of the central nervous system determine the usage of cytotoxic drugs rather than the sensitivity of a specific tumour type to a specific drug. Recently, however, progress has been made in the development of more efficient types of therapy against brain metastases.

show abstract

“…It has previously been reported that certain cases achieved long-term disease control for >13 months with EGFR-TKI re-challenge (40,41). Certain clinical characteristics, including response or time to progression (TTP) to previous EGFR-TKI, chemotherapy between EGFR-TKIs, and EGFR-TKI free interval have been examined as predictive markers for the success of EGFR-TKI re-challenge (16)(17)(18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Plasma T790M and HGF as potential predictive markers for EGFR-TKI re-challenge

et al. 2017

View full text Add to dashboard Cite

Abstract. Re-challenge with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) has been suggested to potentially improve survival in certain populations of patients with advanced lung cancer, but predictive markers for the success of EGFR-TKI re-challenge have not been identified. The present study analyzed 16 re-challenges with EGFR-TKI undertaken in 12 patients with lung adenocarcinoma by investigating T790M and hepatocyte growth factor (HGF) in plasma coupled with clinical characteristics. EGFR mutations in plasma DNA were detected using the wild inhibiting PCR and quenched probe system for exon 19 deletions, and T790M and L858R were detected using the mutation-biased PCR and quenched probe system. HGF levels in the plasma were measured by enzyme-linked immunosorbent assay, and the ratio of HGF levels prior to re-challenge to those prior to the previous EGFR-TKI treatment was calculated. Two re-challenges demonstrated partial response, six remained as stable disease and eight had progressive disease (PD). A total of 4 of the 5 patients with a history of T790M positivity based on plasma DNA levels had PD. A total of 7 of the 8 patients who had ≥1.5-fold elevation of HGF prior to re-challenge with EGFR-TKI suffered PD. Elevation of the HGF ratio to ≥1.5 was significantly associated with poor response to EGFR-TKI re-challenge. Having no history of T790M and an HGF ratio <1.5 was significantly associated with a positive response to EGFR-TKI re-challenge. A combination of T790M detection and HGF quantification using plasma is a potentially useful assay system for predicting the effect of EGFR-TKI re-challenge. Future prospective studies are required to confirm the predictive validity of these markers. IntroductionEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have produced dramatic anti-cancer effects in patients with non-small cell lung cancer (NSCLC) carrying EGFR activating mutations (1-3). The first generation of EGFR-TKIs, including gefitinib and elrotinib, conferred significantly prolonged progression-free survival (PFS) in these patients. The second generation of these drugs, afatinib, brought a remarkable prolongation of overall survival, up to 33 months, in particular in patients with exon 19 deletions (4). In spite of the effectiveness of EGFR-TKIs, patients eventually acquire resistance. Several treatment strategies have been evaluated in clinical trials and practice following the onset of acquired resistance. First, agents targeted at molecules contributing to acquired resistance have been considered. Based on mechanisms including the secondary EGFR mutation, T790M, MET proto-oncogene, receptor tyrosine kinase (MET) amplification, and hepatocyte growth factor (HGF) overexpression, second and third generation EGFR-TKIs and MET inhibitors have been developed (5-9). Afatinib confers a potent anti-cancer effect against lung cancer cells harboring T790M, but a phase 2b/3 randomized trial revealed that the overall response rate and PFS of patients with lung cancer ...

show abstract

Three Cases of Long-Lasting Tumor Control with Erlotinib after Progression with Gefitinib in Advanced Non-Small Cell Lung Cancer

Abstract: Erlotinib may be effective in patients with non-small cell lung cancer who were previously and successfully treated with gefitinib. However, careful selection of these patients is needed.

Cited by 31 publications

References 16 publications

Phase II Study of Gefitinib Readministration in Patients with Advanced Non-Small Cell Lung Cancer and Previous Response to Gefitinib

Phase II Study of Gefitinib Readministration in Patients with Advanced Non-Small Cell Lung Cancer and Previous Response to Gefitinib

Experimental treatment of brain metastases

Plasma T790M and HGF as potential predictive markers for EGFR-TKI re-challenge

Contact Info

Product

Resources

About