Efficacy and risk of cytotoxic chemotherapy in extensive disease-small cell lung cancer patients with interstitial pneumonia.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP. METHODS: We performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016. RESULT: 31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival [OS], 7.1 [95% confidence interval (CI): 0.2-14.0] vs. 10.0 [95% CI: 8.2-11.8] months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP. CONCLUSION: Systemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.

Efficacy of Platinum-Based Chemotherapy for Relapsed Small-Cell Lung Cancer after Amrubicin Monotherapy in Elderly Patients and Patients with Poor Performance Status.

BACKGROUND: Previous studies have shown amrubicin to be an effective first- or second-line treatment option for small-cell lung cancer (SCLC). However, there have been few studies reporting the efficacy of platinum-based chemotherapy after amrubicin therapy. We aimed to evaluate the efficacy of platinum-based chemotherapy as second-line treatment for elderly patients and those with SCLC with poor performance status (PS) previously treated with amrubicin monotherapy. METHODS: The records of SCLC patients who received platinum-based chemotherapy as a second-line chemotherapy after first-line treatment with amrubicin monotherapy were retrospectively reviewed and the treatment outcomes were evaluated. RESULTS: A total of 48 patients were enrolled in this study. Forty-one patients (85%) received carboplatin plus etoposide. The overall response rate was 39.6%. The median progression-free survival and overall survival were 3.7 and 7.6 months, respectively. The efficacy of the platinum-based regimen did not differ with the type of relapse after amrubicin monotherapy. The most common adverse events were hematological toxicities, including grade 3 or 4 neutropenia (38%), leukopenia (33%), and thrombocytopenia (10%). CONCLUSIONS: Platinum-based chemotherapy is potentially a valid treatment option for elderly patients or those with extensive-stage SCLC with poor PS as second-line chemotherapy, who progressed after first-line treatment with amrubicin monotherapy.

Smoking History as a Predictor of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Harboring EGFR Mutations.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) therapy has been recognized as the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, resistance to EGFR-TKIs has been observed in certain subpopulations of these patients. We aimed to evaluate the impact of smoking history on the efficacy of EGFR-TKIs. METHODS: The records of patients (n = 248) with NSCLC harboring activating EGFR mutations who were treated with gefitinib or erlotinib at our institution between March 2010 and June 2016 were retrospectively reviewed, and the treatment outcomes were evaluated. RESULTS: The overall response rate and median progression-free survival (PFS) were 59.7% and 10.7 months, respectively. The overall response rate was significantly higher in the ex- and nonsmokers than in the current smokers (64.6 vs. 51.1%, p = 0.038). PFS also differed significantly between the current smokers and the ex- and nonsmokers (12.4 vs. 7.4 months, p = 0.016). Multivariate analysis identified smoking history as an independent predictor of PFS and overall survival. CONCLUSION: The clinical data obtained in this study provide a valuable rationale for considering smoking history as a predictor of the efficacy of EGFR-TKI in NSCLC patients harboring activating EGFR mutations.

Prognostic differences between oligometastatic and polymetastatic extensive disease-small cell lung cancer.

PURPOSE: Oligometastasis is a state in which cancer patients have a limited number of metastatic tumors; patients with oligometastases survive longer than those with polymetastases. Extensive disease (ED)-small cell lung cancer (SCLC) is considered a systemic disease and a poor survival. This study investigated whether the concept of oligometastases is prognostic factor also applicable to patients with ED-SCLC. METHODS: We performed a retrospective study of 141 consecutive patients with ED-SCLC between 2008 and 2016. The patients were divided into four subgroups: group 1; patients with solitary metastatic site in one organ (n = 31), group 2; patients with 2-5 metastatic sites in one organ (n = 18), group 3; patients with over 6 metastases in one organ (n = 15), and group 4; patients with 2 or more metastatic organs (n = 77). RESULTS: It was identified that 49 patients with ED-SCLC had oligometastases (groups 1 + 2) and 92 had polymetastases (groups 3 + 4). The prognoses of patients with ED-SCLC and oligometastases, defined as ≤5 metastases in a single organ, were significantly superior to those of patients with polymetastases [16.0 (95% CI, 11.0-21.0) months vs. 6.9 (95% CI, 6.0-7.8) months; p<0.001]. 43 of 49 patients with ED-SCLC and oligometastases were relapsed after initial chemotherapy, and 38 (88%) experienced local recurrence. CONCLUSIONS: Patients with ED-SCLC and oligometastases may have improved survival than those with polymetastases. As oligometastatic ED-SCLC tends to recur locally, local therapy combined with systemic chemotherapy may be a treatment option.

Evaluation of osimertinib efficacy according to body surface area and body mass index in patients with non-small cell lung cancer harboring an EGFR mutation: A prospective observational study.

BACKGROUND: Osimertinib is recommended for non-small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M-positive advanced NSCLC who progress on prior EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a prospective observational cohort study. Median BSA and BMI were used as cut-off values to evaluate the impact of body size variables on osimertinib chemotherapy. RESULTS: The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2 , respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression-free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS. CONCLUSION: The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M-positive NSCLC who progress on prior EGFR-TKIs.

Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study.

Purpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation. Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation. Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS. Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.

Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease.

BACKGROUND: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. PATIENTS AND METHODS: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. RESULTS: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59-83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. CONCLUSION: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD.

Comparison of carboplatin plus etoposide with amrubicin monotherapy for extensive-disease small cell lung cancer in the elderly and patients with poor performance status.

BACKGROUND: Carboplatin plus etoposide (CE) is a standard treatment for elderly patients with extensive-disease small cell lung cancer (ED-SCLC). However, amrubicin monotherapy (AMR) may be a feasible alternative. We compared the efficacies and safety profiles of CE and AMR for ED-SCLC in elderly patients and chemotherapy-naive patients with poor performance status (PS). METHODS: The records of SCLC patients who received CE or AMR as first-line chemotherapy were retrospectively reviewed and their treatment outcomes evaluated. RESULTS: Eighty-four patients (median age 72 years; 42 each received CR and AMR) were analyzed; 34 patients had a PS score of 2. There were no significant differences in patient characteristics between the treatment groups. The median progression-free survival rates of patients in the CE and AMR groups were 5.8 and 4.8 months, respectively (P = 0.04); overall survival was 14.0 and 8.5 months, respectively (P = 0.089). Twenty-three CE group patients received AMR as second-line chemotherapy; their median overall survival from first-line chemotherapy was 18.5 months. Grade 3 or higher neutropenia occurred more frequently in patients treated with AMR (64% vs. 40%; P = 0.02), as did febrile neutropenia (14% vs. 7%). CONCLUSIONS: CE remains a suitable first-line treatment for ED-SCLC in elderly patients or those with poor PS in comparison with AMR.