Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study
Abstract Osimertinib is the standard first-line options for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). Co-mutations in TP53 results in poor survival for patients. However, the studies on treatment options and clinical outcomes of patients with EGFR-TP53 co- mutation are...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03422-9 |
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| author | Jixian Li Xiang Zhan Mengqing Shao Renya Zeng Jianan Li Hui Zhu Alei Feng Zhe Yang Wang Jing |
| author_facet | Jixian Li Xiang Zhan Mengqing Shao Renya Zeng Jianan Li Hui Zhu Alei Feng Zhe Yang Wang Jing |
| author_sort | Jixian Li |
| collection | DOAJ |
| description | Abstract Osimertinib is the standard first-line options for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). Co-mutations in TP53 results in poor survival for patients. However, the studies on treatment options and clinical outcomes of patients with EGFR-TP53 co- mutation are limited. Patients with EGFR mutation-positive locally advanced or metastatic NSCLC carrying TP53 mutations were recruited from two institutions and randomly allocated into two groups, either receiving osimertinib plus chemotherapy (Osi + Chemo group) or osimertinib monotherapy (Osi group). The progression-free survival (PFS) was evaluated as the primary endpoint and the response was also assessed. Between January 2020 and August 2023, ninety-eight patients were enrolled with 47 and 51 patients receiving combination therapy and the monotherapy. After a median follow-up of 19.2 months, overall response rate (ORR) was 80.0% vs. 71.7% (p = 0.36), favoring Osi + Chemo group, as well as in disease control rate (DCR) (91.4% vs. 80.4%, p = 0.45). The median PFS in the Osi + Chemo group was 26.0 months versus 20.7 months in the Osi group, but there was no significant difference (p = 0.34). The subgroup analysis indicated that for patients with L858R mutation, Osi + Chemo therapy significantly prolonged the median PFS (not reached [NR] versus 17.1 months, p = 0.03), but showed no benefit in patients with 19Del (20.6 months versus NR, p = 0.31). Osimertinib plus chemotherapy has a tendency to increase ORR and prolong PFS in NSCLC with EGFR and TP53 co-mutations, particularly in patients with L858R mutation. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-9c3260aeae2a4bb780b0f64bb1df4d6c2025-08-20T03:37:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-03422-9Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort studyJixian Li0Xiang Zhan1Mengqing Shao2Renya Zeng3Jianan Li4Hui Zhu5Alei Feng6Zhe Yang7Wang Jing8Shandong Provincial Hospital, Shandong UniversityShandong Provincial Hospital, Shandong UniversityTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityShandong Provincial Hospital, Shandong UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical ScienceTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityShandong Provincial Hospital, Shandong UniversityTumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityAbstract Osimertinib is the standard first-line options for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). Co-mutations in TP53 results in poor survival for patients. However, the studies on treatment options and clinical outcomes of patients with EGFR-TP53 co- mutation are limited. Patients with EGFR mutation-positive locally advanced or metastatic NSCLC carrying TP53 mutations were recruited from two institutions and randomly allocated into two groups, either receiving osimertinib plus chemotherapy (Osi + Chemo group) or osimertinib monotherapy (Osi group). The progression-free survival (PFS) was evaluated as the primary endpoint and the response was also assessed. Between January 2020 and August 2023, ninety-eight patients were enrolled with 47 and 51 patients receiving combination therapy and the monotherapy. After a median follow-up of 19.2 months, overall response rate (ORR) was 80.0% vs. 71.7% (p = 0.36), favoring Osi + Chemo group, as well as in disease control rate (DCR) (91.4% vs. 80.4%, p = 0.45). The median PFS in the Osi + Chemo group was 26.0 months versus 20.7 months in the Osi group, but there was no significant difference (p = 0.34). The subgroup analysis indicated that for patients with L858R mutation, Osi + Chemo therapy significantly prolonged the median PFS (not reached [NR] versus 17.1 months, p = 0.03), but showed no benefit in patients with 19Del (20.6 months versus NR, p = 0.31). Osimertinib plus chemotherapy has a tendency to increase ORR and prolong PFS in NSCLC with EGFR and TP53 co-mutations, particularly in patients with L858R mutation.https://doi.org/10.1038/s41598-025-03422-9NSCLCOsimertinibEGFRTP53Chemotherapy |
| spellingShingle | Jixian Li Xiang Zhan Mengqing Shao Renya Zeng Jianan Li Hui Zhu Alei Feng Zhe Yang Wang Jing Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study Scientific Reports NSCLC Osimertinib EGFR TP53 Chemotherapy |
| title | Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study |
| title_full | Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study |
| title_fullStr | Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study |
| title_full_unstemmed | Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study |
| title_short | Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study |
| title_sort | osimertinib plus chemotherapy versus osimertinib for patients with advanced nsclc with concomitant egfr and tp53 mutations a prospective cohort study |
| topic | NSCLC Osimertinib EGFR TP53 Chemotherapy |
| url | https://doi.org/10.1038/s41598-025-03422-9 |
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