Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009).

Nakamura, Atsushi; Inoue, Akira; Morita, Satoshi; Hosomi, Yukio; Kato, Terufumi; Fukuhara, Tatsuro; Gemma, Akihiko; Takahashi, Kazuhisa; Fujita, Yuka; Harada, Toshiyuki; Minato, Koichi; Takamura, Kei; Kobayashi, Kunihiko; Nukiwa, Toshihiro

doi:10.1200/jco.2018.36.15_suppl.9005

Cited by 99 publications

(83 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To our knowledge, the only published phase III combination therapy trial in EGFR-mutant NSCLC with acquired resistance was the negative IMPRESS trial of chemotherapy with/without gefitinib, 20 although newer phase III data from EGFR-TKI treatment-naive patients are emerging. 21,22 Studies investigating novel agents and combinations to overcome acquired resistance to EGFR-TKIs have not routinely achieved response rates superior to chemotherapy. 23e25 A phase Ib trial combining afatinib and cetuximab showed promising antitumor activity (32% response rate) in patients with T790M-positive NSCLC, but a challenging safety profile.…”

Section: Discussionmentioning

confidence: 99%

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer

et al. 2020

View full text Add to dashboard Cite

Background: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. Patients and methods: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25e75 mg p.o. twice a day; continuous or intermittent), savolitinib (600e800 mg p.o. once a day), or durvalumab (3e10 mg/kg intravenous every 2 weeks). Results: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n ¼ 36), savolitinib (n ¼ 18), or durvalumab (n ¼ 23). Most common adverse events (any grade), occurring in 20% of patients across dose groups, were: selumetinib armddiarrhea (75%), rash (58%), nausea (47%); savolitinib armdnausea (67%), rash (56%), vomiting (50%); durvalumab armdrash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n ¼ 1), 50 mg (n ¼ 1), and 75 mg (n ¼ 4) continuous-dose groups, savolitinib 600 mg (n ¼ 1) and 800 mg dose groups (n ¼ 2), and durvalumab 10 mg/kg (n ¼ 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. Conclusion: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. Clinical trials number: NCT02143466.

show abstract

Section: Discussionmentioning

confidence: 99%

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The opportunities to use liquid biopsy for an analysis of the T790M status may thus also become limited. However, recent studies have shown that combination therapy with a first‐generation EGFR TKI and either platinum‐based chemotherapy or bevacizumab confers a significant survival advantage in comparison with EGFR TKI monotherapy . Moreover, a recent retrospective analysis of the FLAURA trial that examined the mechanisms of acquired resistance to first‐line osimertinib in patients with EGFR ‐mutated advanced NSCLC found that the C797S mutation of EGFR was present at a low frequency (7%) in patients who developed resistance.…”

Section: Discussionmentioning

confidence: 99%

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Takahama

Azuma

Shimokawa

et al. 2020

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Liquid biopsy allows the identification of patients whose tumors harbor specific mutations in a minimally invasive manner. No prospective data have been available for the efficacy of osimertinib in patients with non-small cell lung cancer (NSCLC) who develop resistance to first-or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and who test positive for the TKI resistance-conferring T790M mutation of EGFR by liquid biopsy. Therefore, a phase 2 study was conducted to assess the efficacy and safety of osimertinib in such patients. METHODS: Eligible patients had advanced or recurrent NSCLC with known TKI-sensitizing mutations of EGFR, had documented disease progression after treatment with at least 1 first-or second-generation EGFR TKI, and were positive for the T790M mutation in plasma according to the Cobas EGFR Mutation Test v2 (Roche Diagnostics) or droplet digital polymerase chain reaction analysis. Patients were treated with osimertinib (80 mg/d) until disease progression. The primary endpoint was the overall response rate (ORR) in patients positive for T790M in plasma by the Cobas assay. RESULTS: Between June 2016 and November 2017, 276 patients were screened for their T790M status with a liquid biopsy. Seventy-four patients were positive for T790M in plasma, and 53 of these individuals were enrolled in the study. The ORR for evaluable patients positive for T790M in plasma by the Cobas assay (n = 49) was 55.1% (95% confidence interval [CI], 40.2%-69.3%). The median progression-free survival for all evaluable patients (n = 52) was 8.3 months (95% CI, 6.9-12.6 months). CONCLUSIONS: The results demonstrate the utility of liquid biopsy for the detection of T790M with the Cobas EGFR Mutation Test v2. Plasma genotyping with this assay is informative for treatment selection in clinical practice when tumor sampling is not feasible.

show abstract

“…In particular, patients with a fewer number of metastatic organs after failure of EGFR‐TKI therapy showed a median PPS of more than two years, despite the failure of EGFR‐TKI therapy. This suggests that appropriate use of chemotherapy might yield a good prognosis in selected patients, and that the decrease in the number of metastatic organs after the initial therapy may contribute to the better prognosis, as shown by Nakamura et al . Recently, one randomized phase II study conducted to evaluate the efficacy of local ablative therapy (LAT) for patients with a controlled primary solid tumor and one to five metastatic lesions was reported .…”

Section: Discussionmentioning

confidence: 98%

Number of metastatic organs negatively affects the treatment sequence in patients with EGFR‐TKI failure

Mizuno

Horinouchi²,

Watanabe³

et al. 2020

Thoracic Cancer

View full text Add to dashboard Cite

Background Several studies have previously demonstrated the survival benefit of both EGFR‐TKI treatment and chemotherapy in patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. The aim of the present study was to clarify the factors influencing the treatment sequence after failure of EGFR‐TKI therapy, focusing on the number of organs with metastasis (hereafter, metastatic organs). Methods Between January 2010 and December 2016, consecutive patients with EGFR‐mutated NSCLC who were started on first‐line EGFR‐TKI were reviewed. The factors influencing withholding systemic chemotherapy and the post‐progression survival (PPS) after failure of EGFR‐TKI were investigated. Results A total of 393 patients were started on first‐line EGFR‐TKI during the study period. After excluding patients maintained on EGFR‐TKI or who received osimertinib targeting secondary EGFR T790M, 297 patients were included in the analysis. Among these, 180 (60.6%) received chemotherapy after failure of EGFR‐TKI (TKI‐Ct group), while the remaining 117 (39.4%) received no chemotherapy (TKI‐only group). Multivariate analysis identified older age (≥75 years: odds ratio [OR] = 0.25, 95% confidence interval [CI]: 0.11–0.43, P < 0.001), poor performance status (PS) (≥2: OR = 0.06, 95% CI: 0.03–0.15, P < 0.001), and three or more metastatic organs (OR = 0.42, 95% CI: 0.22–0.80, P = 0.008) as being significantly associated with withholding of chemotherapy after failure of EGFR‐TKI. Conclusion A relatively large number of metastatic organs and a poor PS were associated with the withholding of subsequent chemotherapy after failure of EGFR‐TKI in EGFR‐mutated NSCLC patients. Further research for patients with such a poor prognosis should be investigated in the future.

show abstract

Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009).

Cited by 99 publications

References 0 publications

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer

Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M–positive non–small cell lung cancer: West Japan Oncology Group 8815L/LPS study

Number of metastatic organs negatively affects the treatment sequence in patients with EGFR‐TKI failure

Contact Info

Product

Resources

About