Yosuke Kawashima

Efficacy of bevacizumab and erlotinib combination for leptomeningeal carcinomatosis after failure of erlotinib

In patients with non-small-cell lung cancer harboring an epithelial growth factor receptor (EGFR) active mutation, central nervous system progression after a response to EGFR tyrosine kinase inhibitors is frequent. Central nervous system metastasis, especially leptomeningeal carcinomatosis (LMC), is a serious complication and no standard treatment has been established for LMC. Here, we report two cases in which the addition of bevacizumab to erlotinib enhanced the efficacy against LMC; as a result, radiographic abnormalities decreased markedly and symptoms were well controlled. This combination treatment may be useful to treat LMC in patients with EGFR-positive non-small-cell lung cancer.

Phase II study of amrubicin combined with carboplatin for refractory relapsed small-cell lung cancer: North Japan Lung Cancer Group Trial 0802

BACKGROUND Amrubicin (AMR), a new anthracycline agent, has shown promising results for advanced small-cell lung cancer (SCLC), although the efficacy of AMR alone against refractory relapsed SCLC is insufficient. This study was conducted to evaluate the safety and efficacy of the combination of AMR and carboplatin (CBDCA) in patients with refractory relapsed SCLC. METHODS Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30mg/m(2), days 1-3) and CBDCA (area under the curve 4.0mgmL(-1)min(-1), day 1) every 3 weeks. The primary endpoint of this study was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival, and the toxicity profile. Assuming that an ORR of 45% in eligible patients would indicate potential usefulness and an ORR of 20% would be the lower limit of interest, with α=0.10 and β=0.10, at least 24 patients were required. RESULTS Among 29 eligible patients, the ORR was 34% (90% confidence interval, 20-48). The median PFS was 3.5 months, whereas the median survival time was 7.3 months. The most common grade 3-4 toxicity was neutropenia (79%), although only one patient (3%) suffered from febrile neutropenia. Non-hematological toxicities were of moderate severity and no treatment-related death was observed. CONCLUSIONS This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. However, further investigation of this regimen is warranted.

Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs

Background/Aim: Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed. Patients and Methods: We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs. Results: Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months. Conclusion: This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.

Association of Immune‐Related Adverse Events with Clinical Benefit in Patients with Advanced Non‐Small‐Cell Lung Cancer Treated with Nivolumab

BACKGROUND Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study aimed to evaluate whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS We conducted a retrospective study of patients who received nivolumab monotherapy at Sendai Kousei Hospital (n = 70). The patients were categorized into two groups based on the incidence of irAEs: those with irAEs (irAE group) or those without (non-irAE group). Treatment efficacy was evaluated in each group. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were determined. RESULTS The objective response rate was 57% in the irAE group versus 12% in the non-irAE group. Median progression-free survival was 12.0 months in the irAE versus 3.6 months in the non-irAE group. The incidence of both irAEs and pre-existing antithyroid antibody was significantly higher in responders than in nonresponders. Multivariate analysis identified incidence of irAEs and pre-existing antithyroid antibody as an independent predictor of treatment response. CONCLUSION Objective response rate and progression-free survival were significantly better in the irAE than in the non-irAE group in patients with advanced NSCLC treated with nivolumab monotherapy. The development of irAEs was associated with clinical efficacy, and the presence of pre-existing antithyroid antibody might be correlated with treatment response to nivolumab monotherapy. IMPLICATIONS FOR PRACTICE Immune-related adverse events (irAEs) are frequently observed with nivolumab monotherapy. This study evaluted whether the development of irAEs correlates with treatment response in advanced non-small-cell lung cancer. Results showed that the objective response rate and progression-free survival were significantly better in the patients who developed irAEs than in the patients who did not develop irAEs, and the incidence of irAEs and positivity for antithyroid antibody at pretreatment were independent predictors of treatment response of nivolumab monotherapy. Therefore, the development of irAEs predicts clinical benefit and suggests that cautious management of irAEs can lead to achieving maximum clinical benefit from nivolumab monotherapy.

1476PFINAL RESULTS OF A RANDOMIZED PHASE 2 STUDY COMPARING CARBOPLATIN PLUS IRINOTECAN (CI) VERSUS CARBOPLATIN PLUS AMRUBICIN (CA) FOR EXTENSIVE DISEASE SMALL-CELL LUNG CANCER: NJLCG0901

Y. Tsukita1, N. Morikawa2, S. Sugawara3, M. Maemondo1, T. Harada4, M. Harada5, A. Inoue6, Y. Kawashima3, Y. Fujita7, T. Kato8, H. Yokouchi9, H. Watanabe10, K. Usui11, T. Suzuki12, S. Oizumi13, H. Nagai14, M. Kanbe15, T. Nukiwa16 Department of Respiratory Medicine, Miyagi Cancer Center, Natori, JAPAN Pulmonary Medicine, Allergy and Rheumatology, Iwate Medical University School of Medicine, Iwate, JAPAN Department of Respiratory Medicine, Sendai Kousei Hospital, Sendai, JAPAN Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, JAPAN Department of Pulmonary Disease, National Hospital Organization Hokkaido Cancer Center, Sapporo, JAPAN Department of Respiratory Medicine, Tohoku University, Sendai, JAPAN Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Asahikawa, JAPAN Department of Respiratory Medicine, Kanagawa Cardiovasucular and Respiratory Center, Yokohama, JAPAN Pulmonary Medicine, Fukushima Medical University, Fukushima, JAPAN Respiratory Medicine, Saka Genaral Hospital, Shiogama, JAPAN Division of Respirology, NTT Medical Center Tokyo, Tokyo, JAPAN Division of Respiratory Medicine, Iwate Prefectural Central Hospital, Morioka, JAPAN First Department of Medicine, Hokkaido University School of Medicine, Sapporo, JAPAN Respiratory Medicine, Kyoto University-Graduate School of Medicine, Kyoto, JAPAN Internal Medicine, Senseki Hospital, Shiogama, JAPAN South Miyagi Medical Center, Miyagi, JAPAN