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Background: Immune checkpoint inhibitor plus platinum-etoposide (PE) improved overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). While the CASPIAN trial demonstrated the efficacy of durvalumab plus PE, the clinical trial results may not be representative of the general, real-world population because clinical trials often have strict inclusion and exclusion criteria. We herein report the efficacy and safety of durvalumab plus PE in patients with ES-SCLC in real-world, clinical practice. Methods: The present, monocentric, retrospective study evaluated patients with ES-SCLC or recurrent, limited-stage SCLC who received durvalumab plus PE between September 2020 and February 2023. The efficacy and incidence of adverse events (AEs) were also evaluated. Results: The study included 40 patients, of whom 17 were elderly (age >70 years), and 15 had performance status (PS) 2 or 3. The median follow-up time was 13.0 months [95% confidence interval (CI): 8.0-22.2 months]. The objective response rate was 80.0% (95% CI: 63.1-91.6%), and the disease control rate was 88.6% (95% CI: 73.3-96.8%). The median progression-free survival (PFS) was 5.9 months (95% CI: 4.9-6.9), and the median OS was 25.4 months (95% CI: 4.6-46.2). Factors such as advanced age, poor PS, and presence of brain metastases were not associated with lower PFS and OS. Twenty-six patients (65.0%) experienced grade 3 or higher AEs, mainly hematological toxicity. AEs leading to treatment discontinuation occurred in three patients (8%). Conclusions: Durvalumab plus PE in patients with ES-SCLC showed good efficacy and safety according to our real-world data, suggesting that this treatment is well tolerated in clinical practice, even in elderly patients and those with poor PS.
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Pembrolizumab is a major treatment for recurrent or advanced non-small-cell lung cancer (NSCLC). However, data on its use and pharmacokinetics (PK) in older patients are limited. This open-label, multicenter, observational study evaluated real-world data on the safety, efficacy, and PK of pembrolizumab in older patients with NSCLC. In 99 patients aged ≥75 years, PK was determined by liquid chromatography-mass spectrometry on pretreatment samples. Performance status (PS), geriatric assessment (GA), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The median age was 78 (75-87) years. PS was 2-3 in 14 patients. The median ORR, PFS, and OS were 47.5%, 8.0, and 20.5 months, respectively. Although PK and ORR were not significantly associated, patients with the lowest Cycle 1-trough quartile (Q1) experienced poorer PFS (Q1 vs. Q2-4; 3.4 vs. 11.8 months, P = 0.006) and OS (Q1 vs. Q2-4; 9.9 vs. 21.7 months, P = 0.005) than in other quartiles overall, and even in the PD-L1 ≥50% subset (PFS, Q1 vs. Q2-4; 4.1 vs. 14.7 months, P = 0.005; OS, Q1 vs. Q2-4; 9.4 vs. 22.1 months, P = 0.010). The Q1 subgroup was characterized by poor PS and lower albumin, and more frequent "weight loss ≥ 10%" on the GA. Pembrolizumab therapy had similar PK and efficaciousness in older as well as younger patients. In patients with PS ≥2, low albumin, and vulnerable GA, early increases in PK levels are less likely, potentially diminishing efficacy even when PD-L1 ≥50%.
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Introduction: Previous studies reported an association between immune checkpoint inhibitor infusion timing and the treatment effect in metastatic NSCLC. The present study assessed the association between durvalumab infusion timing and survival outcomes in patients with locally advanced NSCLC. Methods: Patients receiving durvalumab after chemoradiotherapy for locally advanced NSCLC at a single institution were retrospectively analyzed, and the association of the proportion of durvalumab infusions greater than or equal to 20% versus less than 20% after 3 PM with progression-free survival (PFS) and overall survival was assessed. Results: A total of 82 patients were included, with a median age of 69 years (interquartile range, 62-74 years); of these, 67 patients (82%) were of male sex, and 78 patients (95%) had a history of smoking. The median number of durvalumab infusions per patient was 16 (interquartile range, 8-24). Patients with at least 20% of their durvalumab infusions after 3 PM (n = 12/82, 15%) had a significantly shorter PFS than those who did not (median: 7.4 mo versus not available [NA]; hazard ratio [HR], 2.43; 95% confidence interval [CI]: 1.11-5.34, p = 0.027), whereas overall survival was shorter among the former compared with the latter group (median: 22.4 versus NA; HR, 1.80; 95% CI: 0.73-4.42, p = 0.20). In addition, both backward stepwise multivariable analysis and propensity score-matching analysis revealed that receiving at least 20% of durvalumab infusions after 3 PM was significantly associated with worse PFS (HR, 2.54; 95% CI: 1.03-5.67, p = 0.047; and HR, 4.64; 95% CI: 1.95-11.04; p < 0.001, respectively). Conclusions: The time of day of durvalumab infusions may impact survival outcomes in patients with locally advanced NSCLC.
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Osimertinib is the standard of care for patients with epidermal growth factor receptor-activating mutation-positive non-small cell lung cancer. Dose-toxicity has been previously reported, but no dose-response data within the range of 20-240 mg daily (mg/d). Thus, the current 80 mg/d dosing might be too high for elderly Japanese patients with an average body weight of only 50 kg, resulting in excessive toxicity and cost. We therefore initiated a study to investigate whether osimertinib at 40 mg/d is non-inferior to 80 mg/d in patients with advanced or recurrent epidermal growth factor receptor-activating mutation-positive non-small cell lung cancer aged ≥70 years, using a regression discontinuity design. Osimertinib is administered at 40 mg/d for body weight ≤50 kg, and 80 mg/d for body weight >50 kg. The primary endpoint is progression-free survival. Sample size is 550 patients, based on a non-inferiority margin of the progression-free survival hazard ratio 1.333, 0.10 one-sided type I error and 80% power.
Subject(s)
Acrylamides , Aniline Compounds , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Mutation , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Aniline Compounds/administration & dosage , Aniline Compounds/therapeutic use , Acrylamides/administration & dosage , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , ErbB Receptors/genetics , Aged , Female , Male , Aged, 80 and over , Dose-Response Relationship, Drug , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Progression-Free Survival , Indoles , PyrimidinesABSTRACT
Objective The current standard treatment for locally advanced, unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CCRT) and durvalumab administration. Although reports have indicated that the prognosis of squamous cell carcinoma is poorer than that of adenocarcinoma, real-world data are currently inadequate. Methods The present study analyzed patients with stage III NSCLC who received CCRT at the study center between April 2018 and February 2022. These patients were retrospectively classified into adenocarcinoma and squamous cell carcinoma groups for an analysis of the progression-free survival (PFS), overall survival (OS), and patient background factors, including the age, performance status, smoking history, and pre-CCRT laboratory data. Results A total of 109 patients were included for the analysis; 25 were excluded, and 44 and 40 patients were classified into the adenocarcinoma and squamous cell carcinoma groups, respectively. The median PFS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [27.9 (95% confidence interval {CI}: 15.2-not achieved) vs. 9.63 (95% CI: 5.88-13.9) months; p<0.01]. Similarly, the median OS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [not achieved (95% CI: 48.1-not achieved) vs. 23.8 (95% CI; 14.6-not achieved) months; p<0.01]. In the multivariate Cox proportional hazard analysis, the histological type was the only prognostic factor for the PFS (p<0.05) and OS (p<0.05). Conclusion The median PFS and OS were poorer in patients with squamous cell carcinoma than in those with stage III NSCLC treated with CCRT and durvalumab. The histological type was an independent factor affecting the PFS and OS.
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BACKGROUND: A history of pre-administration of immune checkpoint inhibitors has been reported to be associated with good outcomes of ramucirumab (RAM) plus docetaxel (DOC) combination therapy for advanced non-small-cell lung cancer (NSCLC). However, existing knowledge on the clinical significance of RAM and DOC following combined chemoimmunotherapy is limited. Therefore, we evaluated the efficacy and safety of RAM plus DOC therapy after combined chemoimmunotherapy and attempted to identify the predictors of its outcomes. PATIENTS AND METHODS: This multicenter, prospective study investigated the efficacy and safety of RAM plus DOC after combined chemoimmunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. An exploratory analysis measured serum cytokine levels at the start of treatment. RESULTS: Overall, 44 patients were enrolled from 10 Japanese institutions between April 2020 and June 2022. The median PFS and OS were 6.3 and 22.6 months, respectively. Furthermore, the ORR and DCR were 36.4% and 72.7%, respectively. The high vascular endothelial growth factor D (VEGF-D) group had a significantly shorter PFS and OS. A combination of high VEGF-A and low VEGF-D levels was associated with a longer PFS. CONCLUSION: Our results showed that RAM plus DOC after combined chemoimmunotherapy might be an effective and relatively feasible second-line treatment for patients with advanced NSCLC in a real-world setting.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Docetaxel , Lung Neoplasms , Ramucirumab , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Female , Prospective Studies , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged, 80 and over , Immunotherapy/methods , AdultABSTRACT
ALK-positive large-cell neuroendocrine carcinoma (LCNEC) is an exceptionally rare form of lung cancer. The efficacy of ALK inhibitors in treating ALK-positive LCNEC remains unclear. Here, we report a case of ALK-positive LCNEC of the lung, which revealed a sustained clinical benefit (24+ mo of overall survival) after treatment with sequential ALK inhibitors and local therapies. This remarkable improvement in survival underscores the importance of testing metastatic LCNEC for biomarkers, such as ALK rearrangement, using immunohistochemistry or next-generation sequencing, especially in younger patients.
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The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2 ) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30-50 mL/min/1.73 m2 ); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Renal Insufficiency , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Aniline Compounds/adverse effects , Kidney/physiology , Body Weight , Mutation , Protein Kinase Inhibitors/adverse effectsABSTRACT
BACKGROUND: In patients with non-small cell lung cancer (NSCLC) harboring driver alterations, the efficacy of immune checkpoint inhibitors (ICIs) remains uncertain. Our study aimed to examine the first-line ICI efficacy in patients with NSCLC harboring KRAS, MET, FGFR, RET, BRAF, and HER2 alterations in a real-world setting. METHODS: This single-center, retrospective cohort study included patients with advanced NSCLC harboring KRAS, MET, FGFR, RET, BRAF, HER2 alterations or driver-negative, and were treated with first-line ICI therapy. Best overall response, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Seventy-eight patients with NSCLC were included (median age, 72 years): 67% were men, 15% were never-smokers, and 83% had adenocarcinoma. The driver alterations involved KRAS (n = 21), MET (n = 6), FGFR (n = 3), RET (n = 2), BRAF (n = 2), HER2 (n = 1), and driver-negative (n = 43). The partial responses for KRAS, MET, FGFR, RET, BRAF, HER2, and driver-negative were 57%, 50%, 100%, 50%, 100%, 0%, and 47%, respectively. The median PFS (months) was 16.2 (95% confidence interval [CI]: 6.3- not reached [NR]) for KRAS, 2.8 (95% CI: 2.7-NR) for MET, 11.7 (95% CI: 5.9-NR) for other alterations (FGFR, RET, BRAF, and HER2), and 10.0 (95% CI: 3.7-14.3) for driver-negative, respectively. The median OS (months) was 31.3 (95% CI: 9.0-NR) for KRAS, not reached for MET, 23.5 (95% CI: 18.3-NR) for other alterations, and 21.1 (95% CI: 15.2-NR) for driver-negative, respectively. CONCLUSIONS: The benefit of the first-line ICI was similar in advanced NSCLC regardless of the driver alterations, except for MET alterations.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Female , Humans , Immune Checkpoint Inhibitors , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Retrospective StudiesABSTRACT
Background: The baseline tumor size (BTS) is a prognostic factor for patients with non-small cell lung cancer (NSCLC) who received immune checkpoint inhibitor monotherapy (ICI-mono). However, this relationship is not yet known in patients treated with ICI in combination with chemotherapy (ICI-chemo). Methods: This single-center retrospective study evaluated 159 patients with advanced NSCLC who received first-line ICI-mono or ICI-chemo from January 2016 to April 2021. Their BTS values were estimated using the maximum BTS (max BTS) (maximum target lesions' longest diameter) and total BTS (sum of target lesions' longest diameters) in a radiological assessment according to the Response Evaluation Criteria for Solid Tumors. Results: Based on a multivariable analysis, the large max BTS group had worse progression-free survival (PFS) in patients treated with ICI-mono (P=0.009), but it was not associated with worse PFS in patients treated with ICI-chemo (P=0.132). The group treated with ICI-mono had worse PFS compared to the group treated with ICI-chemo in patients with max BTS ≥50 mm (P=0.004), and the group treated with ICI-mono was not associated with worse PFS compared to the group treated with ICI-chemo in patients with max BTS <50 mm (P=0.107). Conclusions: While a large max BTS was identified as a prognostic factor for worse PFS in patients treated with ICI-mono, it was not identified as such in patients treated with ICI-chemo. The max BTS may have different predicting efficacy for patients with NSCLC treated with ICI-mono and ICI-chemo.
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INTRODUCTION: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used as the first-line treatment for EGFR mutation-positive non-small cell lung cancer (NSCLC). Nevertheless, most cases ultimately acquire resistance to osimertinib, and no effective treatment has been currently established for cases having progressive disease (PD) with osimertinib. In clinical practice, EGFR-TKI therapy could be continued beyond response evaluation criteria in solid tumours (RECIST)-defined PD cases when they are clinically stable. Currently, the progression pattern of osimertinib and criteria for identifying patients who might benefit from osimertinib beyond PD are unknown. In addition, the efficacy and safety of osimertinib as the first-line treatment in real-world clinical practice remain unclear in Japan. This multicentre study was designed to evaluate the real-world data on first-line osimertinib and its post-treatment. METHODS AND ANALYSIS: The study enrols patients with EGFR mutation-positive, advanced or recurrent NSCLC who received EGFR-TKI as the first-line therapy after 1 September 2018, from October 2019 to August 2020, and those started on osimertinib will be followed up until August 2022. We will evaluate the efficacy and safety of the first-line osimertinib treatment, adherence to it, progression patterns on RECIST PD and subsequent treatment. ETHICS AND DISSEMINATION: All participating patients will provide written informed consent before entering the study. The protocol, amendments and patients' informed consent forms will be approved before study commencement by the institutional review board or independent ethics committee at each participation site (Lead Ethics Committee; Japan Red Cross Medical Center (26 April 2019, order number 976)). Patients will be anonymised before registration into the study and their anonymised data will be collected from the case report form. The results of this study will be presented at the national and international conferences and submitted for publication. TRIAL REGISTRATION NUMBER: UMIN000038683.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Acrylamides , Aniline Compounds , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Neoplasm Recurrence, Local/pathology , Protein Kinase Inhibitors/therapeutic useABSTRACT
PURPOSE: An increasing number of advanced non-small cell lung cancer (NSCLC) cases are being reported in the ageing population. However, studies on the use of afatinib in elderly patients are scarce. We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters. PATIENTS AND METHODS: The primary end-point was the objective response rate (ORR), and the planned number of registered cases was 35, with a threshold ORR of 50%, an expected ORR of 75%, α of 0.05, and ß of 0.1. Secondary end-points were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (Css) and at the occurrence of clinically significant AEs. RESULTS: The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively. Four patients discontinued because of AEs. Treatment-related death was not observed. No significant change in QOL was observed at baseline and after 4, 8, and 12 weeks. Css was comparable with those in previous reports and was significantly higher in patients with grade 3 AEs. Direct correlations between afatinib treatment and PGx profiles were not observed. CONCLUSIONS: An afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients.
Subject(s)
Afatinib/pharmacology , Afatinib/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/pharmacokinetics , Afatinib/therapeutic use , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Lung Neoplasms/mortality , Male , Progression-Free Survival , Protein Kinase Inhibitors/therapeutic useABSTRACT
BACKGROUND: Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. Here, we conducted a phase II trial of this drug in patients with previously treated MPM. METHODS: Eligible patients with MPM having adequate organ function and a performance status of 0-2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1-3 every three weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events were evaluated as secondary endpoints. RESULTS: This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2-11.2) months, and the median OS was 9.1 (range, 6.2-22.0) months. The median number of treatment cycles was three (range, 2-11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia. CONCLUSIONS: Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.
Subject(s)
Anthracyclines/therapeutic use , Antineoplastic Agents/therapeutic use , Mesothelioma, Malignant/drug therapy , Palliative Care/methods , Pleural Neoplasms/drug therapy , Adult , Aged , Anthracyclines/pharmacology , Antineoplastic Agents/pharmacology , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: The necessity of regular blood tests with the administration of immune checkpoint inhibitors has not been investigated. This study examined the safety of omitting a blood test every 2 weeks for patients with lung cancer who were injected an immune checkpoint inhibitor. METHODS: We conducted a retrospective review of the medical records of 201 patients diagnosed with lung cancer and administered with nivolumab or durvalumab between December 1, 2015, and February 30, 2020, in a single hospital. We extracted 16 patients who had treatments without blood testing every 2 weeks. RESULTS: Adverse events that resulted in discontinued treatment included two cases of interstitial pneumonia, one case of creatinine increase, and one infection. All four cases were detected by chest X-ray or their symptoms. CONCLUSIONS: Our results indicate that immune checkpoint inhibitor administration without a blood test every 2 weeks did not subject patients to more adverse side effects.
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BACKGROUND: Osimertinib exhibits good efficacy in patients with T790M-positive non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Compared with the clinical trials, in real-world clinical practice, osimertinib must be administered to older patients and those with poor Eastern Cooperative Oncology Group performance status (ECOG-PS). Therefore, we investigated the association between osimertinib efficacy/safety and PS score, age, and other clinical features in patients with T790M-positive NSCLC. METHODS: We reviewed all patients with T790M-positive NSCLC and acquired resistance to initial EGFR-TKIs who were administered osimertinib between March 2016 and January 2018 at the Tokyo Metropolitan Cancer and Infectious Diseases Center in Komagome Hospital, Japan. RESULTS: In total, 31 patients, including 8 young (<65 years) and 23 elderly (≥65 years) patients, were included in the study. Of these, 10 (32.3%) patients had poor PS scores. The progression-free survival (PFS) was significantly shorter in young patients was than elderly patients [3.5 vs. 6.4 months, P=0.041; hazard ratio (HR), 2.41]. The overall survival (OS) of the young patients tended to be shorter than that of the elderly patients (5.3 vs. 19.4 months, P=0.067; HR, 2.58). The PFS (9.1 vs. 5.5 months; P=0.071; HR, 0.38) and the OS (not reached vs. 6.6 months, P=0.061; HR, 0.39) were shorter in patients with poor ECOG-PS than those with good ECOG-PS. The toxic effects of osimertinib were manageable. By multivariate analysis, both age and ECOG-PS were independent predictors of osimertinib efficacy. CONCLUSIONS: Poor ECOG-PS and younger age were associated with lower efficacy of osimertinib in T790M-positive NSCLC.
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BACKGROUND: Few studies have investigated the clinical efficacy of third- and later-line of chemotherapy after standard chemotherapy for previously treated advanced non-small cell lung cancer (NSCLC). We prospectively evaluated the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) following standard chemotherapies for previously treated advanced NSCLC. METHODS: The eligible patients having adequate organ functions with performance status 0-2 were enrolled after completing standard chemotherapy. They received weekly nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 every 3 weeks. The primary end point was objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated as secondary end points. RESULTS: This trial was discontinued because of late accrual. Twenty two patients were enrolled from April 2013 and February 2019. The total ORR was 22.7% [95% CI 7.8-45.4] and disease control rate (DCR) was 81.8% [95% CI 59.7-94.8]. Median PFS was 3.4 months [95% CI 2.3-4.1] and median OS was 7.4 months [95% CI 4.2-10.7]. Median follow-up interval was 6.7 months hematological AEs of Grade 3/4 included anemia (18%), leukopenia (18%), and neutropenia (32%), while the most frequent nonhematological AEs were fatigue (50%) and peripheral neuropathy (36.4%). Severe AEs related to treatment were observed in only one patient. CONCLUSION: Nab-paclitaxel may be a safe and effective later-line chemotherapeutic option for previously treated advanced NSCLC after standard of chemotherapies based on other trials.
Subject(s)
Albumins/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Paclitaxel/therapeutic use , Adult , Aged , Albumins/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/pharmacologyABSTRACT
Immuno-checkpoint inhibitor response and immune-related adverse events remain controversial issues. Managing pericardial effusion during programmed cell death 1 inhibitor treatment is challenging. Here, we report a case of successfully managed cardiac tamponade caused by nivolumab-induced pseudoprogression. A 62-year-old male diagnosed with advanced lung adenocarcinoma started on nivolumab. Seven days later, he experienced cardiac tamponade and required pericardiocentesis, and other lesions were larger on computed tomography. The patient's condition stabilized after pericardiocentesis. However, although the lesions other than pericardial effusion were reduced on chest CT, cardiac tamponade recurred after 6 weeks. We considered that the case involved cardiac tamponade induced by pseudoprogression and administered intrapericardial bleomycin after pericardiocentesis. Thereafter, the patient was administered nivolumab for 7 months until disease progression.
Subject(s)
Adenocarcinoma of Lung/drug therapy , Antineoplastic Agents/therapeutic use , Bleomycin/therapeutic use , Cardiac Tamponade/drug therapy , Drug-Related Side Effects and Adverse Reactions/drug therapy , Immunotherapy/adverse effects , Lung Neoplasms/drug therapy , Nivolumab/therapeutic use , Antineoplastic Agents/adverse effects , Cardiac Tamponade/diagnosis , Cardiac Tamponade/etiology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Nivolumab/adverse effects , Pericardiocentesis , Pericardium , Tomography, X-Ray ComputedABSTRACT
PURPOSE: Metastasis of non-small cell lung cancer (NSCLC), indicating hematogenous dissemination, is more frequent in patients harboring epidermal growth factor receptor (EGFR) mutations, who respond dramatically to EGFR-tyrosine kinase inhibitors (TKIs). METHODS: Based on the proposed association of miliary pulmonary metastasis and EGFR mutations in the previous studies, we conducted a retrospective study to assess survival of NSCLC with miliary pulmonary metastases in 223 patients harboring EGFR mutations who were treated with single agent EGFR-TKIs. RESULTS: Progression-free survival (PFS) and overall survival (OS) with single agent EGFR-TKIs were 11.7 months [95% confidence interval (CI) 9.6-13.7] and 23.7 months (95% CI 20.3-26.9), respectively. Patients with and without miliary pulmonary metastases were matched using propensity scores (n = 29 per group) based on clinical characteristics. After matching, the PFS were 8.2 months (95% CI 5.2-15.0) and 14.3 months (95% CI 9.6-30.0) (p = 0.02) in patients with and without miliary pulmonary metastases, respectively. Conversely, the OS were 15.3 months (95% CI 10.6-19.4) and 27.9 months (95% CI 22.0-33.0) (p = 0.003) in patients with and without miliary pulmonary metastases, respectively. By multivariate analysis, miliary pulmonary metastasis was associated with poor prognosis (p = 0.0035). CONCLUSION: The prognosis of patients with advanced NSCLC harboring EGFR mutations with miliary pulmonary metastasis demonstrated significantly worse outcomes compared to those without miliary pulmonary metastasis.