Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial.

BACKGROUND: Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population. METHODS: This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and advanced or metastatic EGFR-mutated NSCLC of any histology, with MET amplification by tissue biopsy fluorescence in-situ hybridisation (FISH; MET gene copy number of ≥5 or MET-to-CEP7 ratio of ≥2) or liquid biopsy next-generation sequencing (MET plasma gene copy number of ≥2·3), following progression on first-line osimertinib. Patients received oral tepotinib 500 mg plus oral osimertinib 80 mg once daily. The primary endpoint was independently assessed objective response in patients with MET amplification by central FISH treated with tepotinib plus osimertinib with at least 9 months of follow-up. Safety was analysed in patients who received at least one study drug dose. This study is registered with ClinicalTrials.gov, NCT03940703 (enrolment complete). FINDINGS: Between Feb 13, 2020, and Nov 4, 2022, 128 patients (74 [58%] female, 54 [42%] male) were enrolled and initiated tepotinib plus osimertinib. The primary activity analysis population included 98 patients with MET amplification confirmed by central FISH, previous first-line osimertinib and at least 9 months of follow-up (median 12·7 months [IQR 9·9-20·3]). The confirmed objective response rate was 50·0% (95% CI 39·7-60·3; 49 of 98 patients). The most common treatment-related grade 3 or worse adverse events were peripheral oedema (six [5%] of 128 patients), decreased appetite (five [4%]), prolonged electrocardiogram QT interval (five [4%]), and pneumonitis (four [3%]). Serious treatment-related adverse events were reported in 16 (13%) patients. Deaths of four (3%) patients were assessed as potentially related to either trial drug by the investigator due to pneumonitis (two [2%] patients), decreased platelet count (one [1%]), respiratory failure (one [1%]), and dyspnoea (one [1%]); one death was attributed to both pneumonitis and dyspnoea. INTERPRETATION: Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated. FUNDING: Merck (CrossRef Funder ID: 10.13039/100009945).

Complete response in a lung adenocarcinoma with pleural metastases initially treated with gefitinib and switched to osimertinib after cerebral oligo-progression with unknown T790M mutation: a case report and review of literature.

BACKGROUND: First- and second-generation anti-epithelial growth factor receptor tyrosine kinase inhibitors have shown great efficacy in the treatment of advanced adenocarcinoma with epithelial growth factor receptor mutations, but this efficacy is limited by certain resistance mechanisms, in particular the T790M mutation, which must be screened before second-line treatment with osimertinib is indicated. The search for this mutation is sometimes difficult, especially in cases of intracranial relapse, through this case report we attempt to discuss the possibility of initiating treatment with osimertinib despite an unknown T790M mutation in such situation. CASE REPORT: We present the case of a 70-year-old Moroccan male patient diagnosed with non-small cell lung carcinoma initially metastatic to the pleura with an epithelial growth factor receptor mutation who received gefitinib in first line with a complete response, he subsequently presented with cerebral oligo-progression with extra cranial stability. The patient was started on osimertinib with unknown T790M status, as it was impossible to perform a cerebral biopsy, the evolution was characterized by a partial response followed by stereotactic radiotherapy then a complete response for 2 years. CONCLUSION: We can discuss osimertinib as an option for patients with stage IV non-small cell lung cancer with brain oligo-progression on prior tyrosine kinase inhibitors and unknown T790M status, further studies are needed in this area.

The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. METHODS: 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. RESULTS: This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK. CONCLUSIONS: This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.

Drug-induced liver injury associated with savolitinib: a novel case report and causality assessment.

BACKGROUND: Savolitinib, a small molecule inhibitor, has gained approval as the inaugural medication in China that specifically targets MET kinase. Patients with advanced non-small cell lung cancer (NSCLC) who show MET exon 14 skipping now have a new and innovative treatment option available. CASE REPORT: In this case report, we describe a patient who experienced drug-induced liver injury (DILI) due to the administration of savolitinib. After being prescribed with savolitinib (400 mg per day, oral), a 73-year-old male diagnosed with stage IV NSCLC with MET exon 14 skipping mutation experienced an increase in liver enzymes and bilirubin levels according to his laboratory tests conducted one month later. Following a 14-day course of hepatoprotective medication, the liver function reverted back to its normal state. After receiving savolitinib (200 mg per day, oral) for one week, the patient was once again diagnosed with severe liver impairment. Then savolitinib was discontinued and received treatment with hepatoprotective drugs for one week. Following the restoration of normal liver function, another attempt was made to administer a small amount of savolitinib (100 mg per day, oral). Thus far, the patient has been followed up and there has been no recurrence of liver damage. Additionally, the lung CT scan revealed ongoing tumor shrinkage with no apparent indications of spreading or metastasis. The Roussel Uclaf Causality Assessment Method (RUCAM) determined that savolitinib was "highly probable" cause of DILI. Moderate-severe was determined to be the extent of DILI severity. CONCLUSION: To the best of our understanding, this is the initial instance of DILI resulting from the use of savolitinib as a standalone treatment in a real-world setting. During the administration of savolitinib, healthcare professionals should carefully consider the potential occurrence of DILI. Administering the patient with a small amount of savolitinib resulted in a remarkable response against the tumor, leading us to speculate that the effectiveness of savolitinib might be associated with its plasma concentration. Studying the pharmacokinetics and pharmacodynamics (PK/PD) of savolitinib is beneficial for tailoring and accurately prescribing the medication to each individual.

A case of response to combination treatment with TSA-DC-CTL immunotherapy and osimertinib in EGFR mutated advanced lung adenocarcinoma.

BACKGROUND: This study details a case of a patient with advanced lung adenocarcinoma harboring an exon 19 deletion in the EGFR gene. METHOD: A 46-year-old female patient was diagnosed with stage IVb left lung adenocarcinoma, with multiple bone and lymph node metastases. Following the identification of tumor-specific antigen peptides, the patient received a combination treatment of immunotherapy (TSA-DC-CTL) and oral osimertinib. Peripheral blood circulating immune cells and circulating tumor cells (CTCs) were monitored before and after treatment. PET-CT and CT scans were used to assess the tumor response to treatment. RESULTS: A significant increase in total lymphocyte percentage and decrease in the number of CTCs in the patient was observed. Imaging studies showed a notable reduction in tumor metastases. CONCLUSION: This report demonstrates the safety and efficacy of TSA-DC-CTL cell immunotherapy combined with osimertinib in the treatment of a patient with advanced lung adenocarcinoma with an EGFR exon 19 deletions. This study describes a promising new treatment option for patients with advanced lung cancer with EGFR mutations.

[Perioperative Targeted Therapy for Operable, Early Stage NSCLC]. / Zielgerichtete Systemtherapie beim operablen Lungenkarzinom.

Non-small cell lung cancer (NSCLC) is characterized by high recurrence rates in the early stages. In a German cohort, recurrence-free survival after 5 years was 62% (stage IA1), 40.7% (stage IIA) and 28% (stage IIIA). In addition to the perioperative use of immune checkpoint inhibitors, targeted tumor therapy is also making inroads as an innovation from the palliative setting into the early stages. Of particular relevance is the use of the EGFR inhibitor osimertinib, which has been shown to improve overall survival in the adjuvant setting. In this practice-oriented review, we briefly describe the current status of adjuvant targeted therapy and the associated testing and provide an outlook on further developments.

A non-enhancing, T2 fluid-attenuated inversion recovery hyperintense, diffusion-restricting brainstem lesion in an EGFR tyrosine kinase inhibitor-treated non-small-cell lung cancer patient.

Leptomeningeal metastasis (LM) is a devastating complication of malignancy. Diagnosis relies on both contrast enhancement on imaging and malignant cells in cerebral spinal fluid cytology. Though early detection and prompt intervention improves survival, the detection of LM is limited by false negatives. A rare brainstem imaging finding uncovered specifically in EGFR mutation-positive lung cancer patients may represent an early sign of LM. This sign demonstrates high signal on T2 fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, but paradoxically lacks correlative contrast enhancement. Here we report a case of a 72-year-old female EGFR-positive lung cancer patient who developed this lesion following treatment with two first-generation EGFR tyrosine kinase inhibitors then showed subsequent response to osimertinib, an irreversible third-generation EGFR tyrosine kinase inhibitor.

A non-enhancing, T2 FLAIR hyperintense, diffusion-restricting brainstem lesion in an EGFR-positive lung cancer patient may represent an early indicator of leptomeningeal metastases.

Near-Complete Response to Osimertinib for Advanced Non-Small-Cell Lung Cancer in a Pretreated Patient Bearing Rare Compound Exon 20 Mutation (S768I + V774M): A Case Report.

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common EGFR mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound EGFR mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients. Out of two mutations, S768I was associated with poor response to third-generation TKI and V774M had unknown clinical significance, highlighting the complexity of the correct management of these kinds of mutations. We reviewed the literature to document the up-to-date preclinical and clinical data concerning third-generation tyrosine kinase inhibitors for the treatment of patients bearing uncommon EGFR mutations.

Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.

INTRODUCTION: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3­DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. METHODS: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). RESULTS: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. CONCLUSION: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

Efficacy and tolerability of capmatinib in a very elderly patient with metastatic NSCLC harboring a MET exon 14 mutation.

We report the case of an 87-year-old female patient who was diagnosed with metastatic non-small-cell lung cancer harboring MET exon 14 skipping mutation (MET ex14) and PD-L1 expression of 60%. A first-line treatment with atezolizumab was started with primary resistance. Then, a second-line treatment with capmatinib, a selective type Ib MET tyrosine kinase inhibitor, was started, achieving a partial response. The patient is still alive and on treatment with capmatinib 300 mg twice daily after 20 months, with a good tolerability and no evidence of disease progression.In summary, our patient experienced a long-lasting response (>18 months) with capmatinib as second-line treatment. Further analyses evaluating the efficacy and tolerability of MET tyrosine kinase inhibitors are warranted, especially in the elderly, a non-small-cell lung cancer population whose tumors could more frequently harbor MET ex14 mutation.

[Box: see text].

Dacomitinib overcomes acquired resistance to osimertinib in advanced NSCLC patients with EGFR L718Q mutation: A two-case report.

RATIONALE: Acquired resistance still inevitably occurs in patients treated with third-generation TKI osimertinib. Although the EGFR L718Q mutation has been reported as a scarce mechanism of osimertinib resistance, advanced therapeutic strategies are still in development. In this report, we included 2 cases of patients who acquired EGFR L858R/L718Q mutation after osimertinib and were overcome by dacomitinib. PATIENT CONCERNS: Case 1: A 77-year-old woman was diagnosed with stage IV lung adenocarcinoma. Case 2: A 64-year-old woman was diagnosed with stage IV lung adenocarcinoma. DIAGNOSES: Case 1: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Since then, treatment with gefitinib was administrated, leading to a progression-free survival of 18 months. The treatment was switched to osimertinib based on the detection of EGFR T790M mutation, resulting in a progression-free survival of 24 months. Subsequently, EGFR L718Q mutation was detected. Case 2: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Icotinib was used as the first-line treatment for 7 months. Osimertinib was applied as the second-line treatment for 13 months based on the EGFR T790M mutation. Subsequently, EGFR L718Q mutation was detected. INTERVENTIONS: Case 1: Dacomitinib was administered. Case 2: Dacomitinib was administered. OUTCOMES: Case 1:The progression-free survival was 8 months. Case 2: The progression-free survival was 3 months. LESSONS: Dacomitinib is a potential treatment option for NSCLC patients with EGFR L718Q mutation after resistance to Osimertinib. Further research is needed to validate the efficacy of Dacomitinib in this context.

Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups. ETHICS AND DISSEMINATION: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION: CRD42022330532.

Prolonged Response to Osimertinib in EGFR-Mutated Metastatic Urothelial Carcinoma, a Case Report.

A 48-year-old woman without obvious environmental risk factors was diagnosed with metastatic urothelial carcinoma harboring a mutation in EGFR typical of driver mutations for non-small cell lung cancer. Within a year, her cancer progressed on four standard therapies for urothelial cancer, including cancer in lungs, liver, bone, and brain. As fifth-line therapy, she received osimertinib, leading to a complete response in the brain and improvement elsewhere, and the cancer remained controlled for six months. Targeted therapy for rare driver mutations can be effective in urothelial cancer and should be considered prior to exhausting standard therapies.

EGFR-TKI-induced Factor V deficiency in a patient with advanced non-small cell lung cancer: The first case report.

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is routinely prescribed as first-line therapy for advanced non-small cell lung cancer, regardless of the presence of the T790M resistance mutation. This study reports a rare case of Factor V inhibitor detection during osimertinib therapy in a patient with lung adenocarcinoma. These findings underscore the importance of vigilant monitoring for coagulation abnormalities during EGFR-TKI therapy.

A phase II study of osimertinib in patients with NSCLC harboring EGFR exon 20 insertion: A multicenter trial of the Korean Cancer Study Group (LU17-19).

BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertions account for up to 10% of all EGFR mutations. Clinical outcomes in patients receiving approved EGFR exon 20 insertion-specific inhibitors have been variable. Although osimertinib has demonstrated antitumor activity in clinical trials, its clinical efficacy and translational potential remain to be determined in non-small cell lung carcinoma (NSCLC) with EGFR exon 20 insertion. METHODS: In this multicenter phase II study, patients with advanced NSCLC harboring EGFR exon 20 insertions for whom the standard chemotherapy failed received 80 mg osimertinib once daily. The primary endpoint was the investigator-assessed objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile. RESULTS: Among 15 patients enrolled at stage 1, the best response was most commonly disease stabilization (73.3 %), which did not meet the stage 1 threshold (objective response ≥ 2/15). As of data cutoff, two patients remained on the treatment. The median PFS and OS were 3.8 (95 % confidence interval [CI] = 1.7-5.5) months and 6.5 (95 % CI = 3.9-not reached) months, respectively. Adverse events (≥grade 3) were anemia, hypercalcemia, and pneumonia (13.3 % each), and asthenia, femur fracture, increased alkaline phosphate, hyperkalemia, bone pain, and azotemia (6.7 % each). Pre-existing EGFR C797S mutation detected in plasma limited the efficacy of osimertinib. CONCLUSION: Osimertinib at 80 mg once daily had limited efficacy and mostly showed disease stabilization with an acceptable safety profile in advanced NSCLC harboring EGFR exon 20 insertions. CLINICALTRIALS: govIdentifier: NCT03414814.

Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study.

OBJECTIVE: Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. METHODS: From September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. RESULTS: The ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported. CONCLUSION: This study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.

EGFR V834L and L858R Comutation Is Associated With Response to Osimertinib in Non-Small-Cell Lung Cancer.

Up-front osimertinib leads to clinical benefit in EGFR V834L and L858R comutated NSCLC.

Single-molecule targeted therapy shrinks lung lesions and improves bone metastases: A case report.

RATIONALE: Bone metastasis is a common metastatic mode of advanced lung cancer and poses a great threat to the survival and quality of life of patients with this disease. However, the available literature has limited treatment options for advanced lung cancer with bone metastases. PATIENTS CONCERNS: A 76-year-old married male patient was underwent CT due to cough and sputum for 1 month. On CT, space-occupying lesions were found in the left inferior lobe of the lung, as well as multiple bone metastases in the vertebral body and ilium. DIAGNOSES: Pathologic sectioning of the lung lesion after puncture revealed invasive lung adenocarcinoma, and a genetic test revealed EGFR exon 21: L858R (64.60%). INTERVENTIONS: Considering that the disease was not suitable for radiotherapy (extensive metastasis) and could not be treated with chemotherapy (poor underlying condition), the patient was given molecularly targeted therapy with osimertinib. OUTCOMES: After 10 months of standard treatment (80 mg orally, once a day), the lung lesions of the patients became significantly smaller, and the bone metastases distinctly improved. And the patient's condition has not shown any signs of rebound with the one-year follow-up. LESSONS SUBSECTIONS: In the present case, the bone metastases from lung adenocarcinoma almost completely disappeared after treatment with a single molecular targeted therapy agent, increasing the confidence in the treatment of advanced lung cancer.