Osimertinib for patients with EGFR T790M mutation-positive non–small-cell lung cancer and a poor performance status

Nakashima, Kazuhisa; Kimura, Masashi; Akamatsu, Hiroaki; Daga, Haruko; Imai, Hisao; Taira, Tetsuhiko; Ko, Ryo; Hisamatsu, Yasushi; Nishino, Kazumi; Sugimoto, Takeya; Miyashita, Yosuke; Takahashi, Toshiaki

doi:10.1093/jjco/hyz041

Cited by 21 publications

(12 citation statements)

References 18 publications

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“…Median duration of the sequential treatment strategy was 31.3 months in patients with ECOG 0-1 and 22.2 months in patients with ECOG ≥ 2 (p < 0.001) [13]. Recently, results of osimertinib treatment in a group of 30 patients with moderate performance status (ECOG 2-3) have been published, in which 53% of patients attained objective responses to treatment and median PFS was 8.2 months [14]. The majority of the subjects (63%) had an improvement in their general condition and the rates of adverse reactions and treatment-related deaths were in line with expectations based on other reports in the literature.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

Knetki-Wróblewska

Kowalski

Czyżewicz

et al. 2020

Advances in Respiratory Medicine

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Introduction: Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated efficacy in the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) in prospective clinical trials. Material and methods: This retrospective analysis evaluated the outcomes of 32 pretreated patients with EGFR T790M mutation who received osimertinib in clinical practice at seven centers in Poland within the Expanded Drug Access Program. Osimertinib was used in the second line in 59% of patients and in later lines in 41%. Results: Objective response was attained in 16 patients (50%), and 12 subjects (38%) had stable disease. Median progression-free survival was 11.3 months in the overall population, 12.6 months in patients with EGFR exon 19 mutation and 7.5 months in patients with EGFR exon 21 mutation (p = 0.045). Median overall survival (OS) was 18.3 months. Overall, 58.4% and 45.6% of patients remained in follow-up after 12 and 24 months, respectively. Median OS appeared longer for patients without cerebral metastases than for those with cerebral metastases (27.4 vs 9.4 months, respectively; p = 0.078), and for patients with the Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 than those with ECOG PS 2 (27.4 vs 11.8 months, respectively; p = 0.189), although neither result reached statistical significance. Median OS of patients with partial response, stable disease and progressive disease was 27.4, 12.7 and 4.5 months, respectively (p < 0.001). Age, comorbidities, line of treatment with osimertinib, and type of activating EGFR mutation did not impact on OS. Adverse events of any grade or grade 3/4 were reported in 38% and 9% of patients, respectively. One person discontinued due to interstitial pneumonia. Conclusion: These results confirm the value of osimertinib in patients with previously treated EGFR T790M-mutant NSCLC. Clinical benefit was evident in patients with cerebral metastases and moderate performance status.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

Knetki-Wróblewska

Kowalski

Czyżewicz

et al. 2020

Advances in Respiratory Medicine

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“…First, the cohort size was very small (18 patients). Moreover, our present study included only two patients with a PS score of 4, while our previous retrospective study included no patients with a PS score of 4 [14]. Therefore, the potential clinical benefit of osimertinib for patients with PS score of 4 remains unclear.…”

Section: Discussionmentioning

confidence: 88%

“…The median PFS was approximately 3 months for the carboplatin plus paclitaxel therapy for Japanese patients with NSCLC and PS 2 [18]. In our previous study, the median PFS was 8.2 months for osimertinib therapy for patients with NSCLC and poor PS [14]. Therefore, the PFS threshold of 3.0 months and an expected PFS of 8.2 months was set for the present study.…”

Section: Discussionmentioning

confidence: 97%

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Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial

et al. 2020

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Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center, single-arm phase II study to evaluate its efficacy and safety in EGFR T790M mutation-positive NSCLC patients with Eastern Cooperative Oncology Group PS scores of between 2 and 4. Patients received 80 mg of osimertinib once daily. Our primary endpoint was progression-free survival. Eighteen patients were enrolled between June 2017 and November 2018. The median age was 77 years (range: 55-85 years). Ten, six, and two patients had PS scores of 2, 3, and 4, respectively. All patients had adenocarcinoma with common EGFR mutations and had been treated with first-or second-generation EGFR-tyrosine kinase inhibitors previously. The overall median progression-free survival was 7.0 months (90% confidence interval: 5.5-8.9 months). The overall response rate and median overall survival were 53% and 12.7 months, respectively. Moreover, improved PS scores were observed in 72% of the patients. Although the incidence of grade 3 adverse events was low, with no grade 4 or 5 events observed, three patients required treatment cessation due to the development of interstitial lung disease. Osimertinib therapy could be beneficial for EGFR T790M mutation-positive advanced NSCLC patients with poor PS. This trial was registered with the Japan Registry of Clinical Trials on March 12, 2019 (trial no. jRCT1041180081).

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“…A study conducted using real‐world data before the launch of osimertinib revealed that there was no difference in OS between second‐line treatments and that ECOG PS was a prognostic factor 26 . ECOG PS improved in T790M‐positive lung cancer patients after treatment with osimertinib 27 . However, real‐world data showed that the median OS (9 months) of patients with ECOG PS ≥2 patients treated with osimertinib as second‐line therapy was shorter than patients with ECOG PS 0 or 1 28 …”

Section: Discussionmentioning

confidence: 99%

Second‐line therapy with first‐ or second‐generation tyrosine kinase inhibitors in EGFR‐mutated non‐small cell lung cancer patients with T790M‐negative or unidentified mutation

et al. 2021

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Background T790M mutation causes resistance to tyrosine kinase inhibitors (TKIs) in approximately 49% of patients with epidermal growth receptor‐mutant non‐small cell lung cancer (NSCLC). The cause of resistance in the remaining half of the cases is a minor mutation or unknown. Here, we conducted a retrospective study of epidermal growth receptor‐mutant NSCLC patients with T790M‐negative or an unidentified mutation to appraise the therapeutic response to first‐ or second‐generation tyrosine kinase inhibitors as a second‐line treatment. Methods The study included 39 patients treated in our institution from April 2012 through March 2020 with second‐line tyrosine kinase inhibitors or chemotherapy after completing a first‐line therapy with tyrosine kinase inhibitors. Results The patients were allocated to two groups: chemotherapy (n = 28) and a tyrosine kinase inhibitor (n = 11) groups. The median progression‐free survival (PFS) was 5.4 months in the chemotherapy group and 3.4 months in the tyrosine kinase inhibitor group (p‐value = 0.36), while the median overall survival (OS) was 16.1 months in the chemotherapy group and 12.8 months in the tyrosine kinase inhibitor group (p‐ value = 0.20). This study showed no significant difference in PFS and OS between the chemotherapy and tyrosine kinase inhibitor groups. Conclusions These observations suggest that first‐ and second‐generation tyrosine kinase inhibitors are not recommended for second‐line treatment in epidermal growth factor receptor‐mutated NSCLC patients with T790M‐negative mutation who have received tyrosine kinase inhibitors as first‐line treatment.

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Osimertinib for patients with EGFR T790M mutation-positive non–small-cell lung cancer and a poor performance status

Cited by 21 publications

References 18 publications

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

Effectiveness of Osimertinib in Patients with Lung Adenocarcinoma in Clinical Practice—The Expanded Drug Access Program in Poland

Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial

Second‐line therapy with first‐ or second‐generation tyrosine kinase inhibitors in EGFR‐mutated non‐small cell lung cancer patients with T790M‐negative or unidentified mutation

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