Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer
Abstract Background The epidermal growth factor receptor (EGFR) mutation is a risk factor associated with brain metastases (BMs) in patients with non‐small cell lung cancer (NSCLC). This study aimed to evaluate the impact of osimertinib early dose reduction on BM worsening. Methods We retrospectivel...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6393 |
| _version_ | 1797672421791105024 |
|---|---|
| author | Takehiro Tozuka Rintaro Noro Akihiko Miyanaga Shinji Nakamichi Susumu Takeuchi Masaru Matsumoto Kaoru Kubota Kazuo Kasahara Masahiro Seike |
| author_facet | Takehiro Tozuka Rintaro Noro Akihiko Miyanaga Shinji Nakamichi Susumu Takeuchi Masaru Matsumoto Kaoru Kubota Kazuo Kasahara Masahiro Seike |
| author_sort | Takehiro Tozuka |
| collection | DOAJ |
| description | Abstract Background The epidermal growth factor receptor (EGFR) mutation is a risk factor associated with brain metastases (BMs) in patients with non‐small cell lung cancer (NSCLC). This study aimed to evaluate the impact of osimertinib early dose reduction on BM worsening. Methods We retrospectively analyzed EGFR‐mutant NSCLC patients treated with osimertinib as first‐line treatment between August 2018 and October 2021. To evaluate the impact of osimertinib early dose reduction, we performed a landmark analysis of patients who achieved disease control at 4 months. Patients were divided into two groups according to whether the osimertinib dose was reduced or not, within 4 months after the start of treatment. We evaluated the time to BMs onset or progression, progression‐free survival, and overall survival. Results In total, 62 NSCLC patients with EGFR mutations were analyzed. Thirteen patients experienced early dose reduction of osimertinib treatment. Seven patients received osimertinib 40 mg daily, and six received 80 mg every other day. The most common reason for dose reduction was gastrointestinal toxicity (n = 4), followed by skin rashes (n = 3). The time to BMs onset or progression was significantly shorter in patients who experienced early dose reduction than in those who continued regular treatment (Hazard ratio 4.47, 95% confidence interval, 1.52–13.11). The 1‐year cumulative incidence of BM onset or progression was 23.1% in the reduced‐dose group and 5.0% in the standard dose group. The risk of worsening BMs with early dose reduction of osimertinib treatment was higher in patients who had BMs before treatment and in younger patients. Conclusion Early dose reduction of osimertinib was a risk factor for the worsening of BMs. A higher risk was associated with younger patients and those presenting BMs before treatment. |
| first_indexed | 2024-03-11T21:29:48Z |
| format | Article |
| id | doaj.art-54843e42ca924dc5a5ec2837bb1b4e48 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-11T21:29:48Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-54843e42ca924dc5a5ec2837bb1b4e482023-09-27T11:46:08ZengWileyCancer Medicine2045-76342023-09-011217177311773910.1002/cam4.6393Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancerTakehiro Tozuka0Rintaro Noro1Akihiko Miyanaga2Shinji Nakamichi3Susumu Takeuchi4Masaru Matsumoto5Kaoru Kubota6Kazuo Kasahara7Masahiro Seike8Department of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine Nippon Medical School Tokyo JapanAbstract Background The epidermal growth factor receptor (EGFR) mutation is a risk factor associated with brain metastases (BMs) in patients with non‐small cell lung cancer (NSCLC). This study aimed to evaluate the impact of osimertinib early dose reduction on BM worsening. Methods We retrospectively analyzed EGFR‐mutant NSCLC patients treated with osimertinib as first‐line treatment between August 2018 and October 2021. To evaluate the impact of osimertinib early dose reduction, we performed a landmark analysis of patients who achieved disease control at 4 months. Patients were divided into two groups according to whether the osimertinib dose was reduced or not, within 4 months after the start of treatment. We evaluated the time to BMs onset or progression, progression‐free survival, and overall survival. Results In total, 62 NSCLC patients with EGFR mutations were analyzed. Thirteen patients experienced early dose reduction of osimertinib treatment. Seven patients received osimertinib 40 mg daily, and six received 80 mg every other day. The most common reason for dose reduction was gastrointestinal toxicity (n = 4), followed by skin rashes (n = 3). The time to BMs onset or progression was significantly shorter in patients who experienced early dose reduction than in those who continued regular treatment (Hazard ratio 4.47, 95% confidence interval, 1.52–13.11). The 1‐year cumulative incidence of BM onset or progression was 23.1% in the reduced‐dose group and 5.0% in the standard dose group. The risk of worsening BMs with early dose reduction of osimertinib treatment was higher in patients who had BMs before treatment and in younger patients. Conclusion Early dose reduction of osimertinib was a risk factor for the worsening of BMs. A higher risk was associated with younger patients and those presenting BMs before treatment.https://doi.org/10.1002/cam4.6393brain metastasesdose reductionnon‐small cell lung cancerosimertinib |
| spellingShingle | Takehiro Tozuka Rintaro Noro Akihiko Miyanaga Shinji Nakamichi Susumu Takeuchi Masaru Matsumoto Kaoru Kubota Kazuo Kasahara Masahiro Seike Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer Cancer Medicine brain metastases dose reduction non‐small cell lung cancer osimertinib |
| title | Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer |
| title_full | Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer |
| title_fullStr | Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer |
| title_full_unstemmed | Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer |
| title_short | Osimertinib early dose reduction as a risk to brain metastasis control in EGFR‐mutant non‐small cell lung cancer |
| title_sort | osimertinib early dose reduction as a risk to brain metastasis control in egfr mutant non small cell lung cancer |
| topic | brain metastases dose reduction non‐small cell lung cancer osimertinib |
| url | https://doi.org/10.1002/cam4.6393 |
| work_keys_str_mv | AT takehirotozuka osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT rintaronoro osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT akihikomiyanaga osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT shinjinakamichi osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT susumutakeuchi osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT masarumatsumoto osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT kaorukubota osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT kazuokasahara osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer AT masahiroseike osimertinibearlydosereductionasarisktobrainmetastasiscontrolinegfrmutantnonsmallcelllungcancer |