Amrubicin Monotherapy Research Articles

220P Treatment outcomes of amrubicin monotherapy for patients with advanced hepatobiliary and pancreatic neuroendocrine carcinoma

220P Treatment outcomes of amrubicin monotherapy for patients with advanced hepatobiliary and pancreatic neuroendocrine carcinoma

Efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma

The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of second-line chemotherapy in patients with pulmonary LCNEC. We retrospectively reviewed patients with pulmonary LCNEC or possible LCNEC (pLCNEC) who received platinum-based chemotherapy as the first-line treatment. Among these patients, we evaluated the efficacy of second-line treatment by comparing patients with small cell lung cancer (SCLC group). Of the 61 patients with LCNEC or pLCNEC (LCNEC group) who received first-line chemotherapy, 39 patients were treated with second-line chemotherapy. Among the 39 patients, 61.5% received amrubicin monotherapy. The median progression-free survival (PFS) and overall survival (OS) in the LCNEC groups were 3.3 and 8.3 months, respectively. No significant differences in the PFS (hazard ratio [HR]: 0.924, 95% confidence interval [CI] 0.647–1.320; P = 0.664) and OS (HR: 0.926; 95% CI 0.648–1.321; P = 0.670) were observed between the LCNEC and SCLC groups. In patients treated with amrubicin, the PFS (P = 0.964) and OS (P = 0.544) were not different between both the groups. Second-line chemotherapy, including amrubicin, may be considered as a treatment option for patients with pulmonary LCNEC.

Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study.

BackgroundTopoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors.MethodsThis study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method.ResultsA total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 vs. 2.5 months; P=0.034).ConclusionsThese results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.

Efficacy and safety of amrubicin monotherapy after atezolizumab plus carboplatin and etoposide in patients with relapsed small-cell lung cancer

This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with atezolizumab plus carboplatin and etoposide (AteCE). This retrospective study evaluated patients with relapsed SCLC who were treated with previously AteCE combination therapy followed by amrubicin monotherapy between August 2019 and May 2021. Clinical efficacy and toxicity were analyzed. Overall, 40 patients were included: 12 and 28 patients had sensitive and refractory relapse, respectively. The response rate was 32.5% (25.0% in the sensitive group and 35.7% in the refractory group). The median progression-free survival (PFS) and overall survival (OS) from the first amrubicin treatment was 3.4 months (95% CI: 1.9–4.9 months) and 9.9 months (95% CI: 4.5–11.5 months), respectively. There was no significant between-group difference in median PFS (3.6 months vs. 3.2 months, p = 0.42) or median OS (11.2 months vs. 7.3 months, p = 0.78). Grade ≥ 3 hematological adverse events occurred as follows: decreased white blood cells in 52.5% of patients; decreased neutrophil count in 57.5%; and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. There were no treatment-related deaths. Amrubicin is feasible and effective for relapsed SCLC patients previously treated with AteCE therapy. Although immune checkpoint inhibitor treatment (ICI) does not improve the effect of amrubicin, the toxicity is not increased, suggesting that amrubicin remains effective even after ICI administration. Thus, amrubicin after AteCE could be the preferred standard chemotherapeutic choice in patients with relapsed SCLC.

MA16.02 Platinum-Doublets as Second-Line Treatment for Relapsed Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Second-line chemotherapy regimens for patients with relapsed small-cell lung cancer are very limited. In real world practice, re-challenge chemotherapy with first-line platinum-doublets has been commonly used in addition to topotecan or amrubicin monotherapy. However, whether platinum-doublet chemotherapy is an appropriate option as second-line treatment remains unclear. Data to generalize the efficacy of platinum-doublet chemotherapy as second-line treatment in comparison with the monotherapy regimens were of high interest.

Impact on second-line treatment after failure of immune checkpoint inhibitor (ICI) combination chemotherapy in extensive-disease small cell lung cancer: Experience of the Okayama Lung Cancer Study Group.

e20590 Background: For patients with extensive-disease small cell lung cancer (ED-SCLC), amrubicin monotherapy is an important therapy in the treatment of recurrence, but there has been no adequate evaluation of how effective it actually is after failure of first-line chemotherapy including immune checkpoint inhibitor (ICI). Therefore, the purposes of this study are to determine the proportion of patients who received amrubicin monotherapy in the treatment of relapse after first-line treatment with ICI (arm A) and to investigate the efficacy of amrubicin therapy after arm A compared with after chemotherapy without ICI (arm B). Methods: Consecutive 40 pts with ED-SCLC NSCLC were retrospectively assessed who underwent ICI-containing chemotherapy (n = 19) or standard cytotoxic chemotherapy (n = 21) in the 1st-line setting between 2017 and 2020. Results: In arm A, 3 of 19 patients (16%) were still on first-line ICI maintenance therapy, 2 (2/19; 11%) had ICI treatment adverse events (interstitial pneumonia, cardiopulmonary arrest), and 1 patient could not receive second-line therapy due to a decrease in performance status (PS) to 3. In arm B, 11 of 21 patients (52%) did not receive amrubicin as second-line therapy, including 1 patient with worsening PS, 1 patient with adverse events (hematologic toxicity), 1 patient refusal, and 6 patients with combination of ICI and chemotherapy. 23 patients (arm A; 13 (57%), arm B; 10 (43%)) were able to receive amrubicin monotherapy, including 7 patients (6 cases vs 1 case) were sensitive relapses, and 16 (7 vs 9 cases) were refractory relapses. There was no significant difference in either PFS or survival after first-line treatment in 16 patients with refractory relapse who received amrubicin as second-line treatment (PFS: 4.8 vs 5.2 months, p = 0.51), (median survival after first-line treatment: 9.6 vs 12.8, p = 0.75). Conclusions: Patients who received ICI in the first-line treatment were fully eligible to receive amrubicin in the second-line treatment. The recurrence pattern tended to be sensitive relapse and we found that the efficacy of amrubicin in refractory relapse was not affected by the administration of ICI in the first-line treatment.

Platinum-doublet chemotherapy as second-line treatment for relapsed patients with small-cell lung cancer: A systematic review and meta-analysis

ObjectiveOptimal second-line chemotherapy for patients with relapsed small-cell lung cancer remains debatable. In addition to topotecan or amrubicin monotherapy, re-challenge with first-line platinum-doublets have been commonly used. In this study, we investigated whether platinum-doublets are suitable as second-line treatment for relapsed small-cell lung cancer. Materials and methodsStudies that enrolled relapsed small-cell lung cancer and compared platinum-doublets with non-platinum-based regimens for second-line treatment were identified using PubMed and EMBASE. A meta-analysis was conducted to calculate the relative risk of objective response rate and disease control rate of the second-line chemotherapy. Subgroup analyses were conducted to focus on comparison with standard second-line regimens and sensitive relapse. Progression-free and overall survival, and adverse events were systematically reviewed. ResultsTen studies published between 2011 and 2020 were included in our analysis with a total of 1222 patients: 438 treated with platinum-doublets and 784 with non-platinum-based regimens. The objective response rates for second-line platinum-doublet and non-platinum regimens were 47.3 % [95 % CI: 40.5–54.0] and 31.5 % [95 % CI: 22.2–40.8], respectively. Patients treated with platinum-doublets had a significantly higher objective response rate than patients with non-platinum-based regimens (RR [95 % CI]: 1.527 [1.100–2.121], p = 0.011), as well as disease control rate (RR [95 % CI]: 1.152 [1.052–1.262], p = 0.002). In a subgroup analysis comparing platinum-doublets with topotecan or amrubicin, patients treated with platinum-doublets had significantly higher objective response rate and disease control rate (RR [95 % CI]: 1.663 [1.055–2.619], p = 0.028 and 1.170 [1.021–1.340], p = 0.023 respectively). Progression-free and overall survival appeared consistent with the tumor responses. Adverse events associated with platinum-doublets appeared acceptable compared with the monotherapies. ConclusionPlatinum-doublet chemotherapy as second-line treatment for patients with relapsed small-cell lung cancer can be considered as a reasonable option in comparison with non-platinum regimens.

Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure.

Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy.Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital.Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections.Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.

Impact of Amrubicin Monotherapy as Second-Line Chemotherapy on Outcomes in Elderly Patients with Relapsed Extensive-Disease Small-Cell Lung Cancer.

PurposeAmrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after chemotherapy by carboplatin plus etoposide (CE) has not been sufficiently evaluated.Patients and MethodsThe medical records of patients with relapsed SCLC who received AMR as second-line chemotherapy were retrospectively reviewed, and their treatment outcomes were evaluated.ResultsForty-one patients with a median age of 76 years were analyzed. The overall response rate was 26.8%. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 8.1 months, respectively. While the median PFS of 4.7 and 2.8 months in the sensitive relapse and the refractory relapse group differed significantly (P=0.043), respectively, the median OS of 10.7 and 6.8 months in the respective relapse groups did not indicate a statistically significant difference (P=0.24). The median PFS in a group with a modified Glasgow prognostic score (mGPS) of 0 and a group with a mGPS 1 or 2 were 4.5 and 1.6 months (P=0.052), respectively, and the median OS in the respective mGPS groups were 10.7 and 4.4 months (P=0.034). Multivariate analysis identified good performance status, limited disease, and mGPS 0 as favorable independent predictors of PFS and OS of AMR monotherapy. Grade 3 or higher neutropenia was observed in 23 patients (56%), and febrile neutropenia was observed in nine patients (22%). Non-hematological toxic effects were relatively mild, and pneumonitis and treatment-related deaths were not observed.ConclusionAMR is an effective and feasible regimen for elderly patients with relapsed SCLC after CE therapy.

Post-progression survival is strongly linked to overall survival in refractory small-cell lung cancer patients who received amrubicin.

The benefits of second-line chemotherapy on the overall survival (OS) of small-cell lung cancer (SCLC) patients might be confounded by subsequent therapies. In this study, we aimed to determine the influence of progression-free survival (PFS) and postprogression survival (PPS) on OS after second-line chemotherapy in patients with refractory SCLC treated with amrubicin monotherapy. We analyzed the data of 35 patients with refractory SCLC who were treated with amrubicin monotherapy as second-line chemotherapy between July 2005 and December 2015. The correlations of PFS and PPS with OS were statistically analyzed at the individual level using Spearman's rank correlation and linear regression analyses. The correlation between PPS and OS was strong (r = 0.88, P < 0.05, R2 = 0.87), while that between PFS and OS was weak (r = 0.60, P < 0.05, R2 = 0.15). The number of regimens administered after disease progression postsecond-line chemotherapy was significantly associated with PPS (P = 0.003). OS is more strongly linked to PPS than to PFS in refractory SCLC patients who undergo amrubicin monotherapy as a second-line treatment. These results suggest that treatments administered after second-line chemotherapy affect the OS of refractory SCLC patients treated with amrubicin monotherapy.

EP1.06-01 Amrubicin Treatment as Palliative-Intended Chemotherapy for Previously Treated Malignant Pleural Mesothelioma

Treatment options for non-naive malignant pleural mesothelioma (MPM) are limited. Few phase II trials have provided evidence for the treatment. Till date, antineoplastic activity has been observed in phase II trials in patients with MPM treated with anthracyclines, doxorubicin, or pegylated-liposomal doxorubicin. However, few studies have reported on these treatments because of severe toxicities. Conversely, amrubicin (AMR) is an anthracycline drug that is commonly used for treating thoracic tumors; therefore, we know that the treatment is generally well tolerated. We performed this phase II trial to determine whether AMR monotherapy is a promising treatment approach for non-chemotherapy naive patients with MPM. Non-randomized phase II trial Patients diagnosed with MPM based on the histological and cytological examination of specimens, with disease progression after pemetrexed/platinum, 1–2 prior regimens, age 18–74 years, AMR naïve status, and performance status (PS) 0–2 were enrolled. Patients received 35 mg/m2 AMR (days 1–3) every 3 weeks until tumor progression and had unacceptable toxicities. The primary endpoint was tumor response rate, and secondary endpoints were progression-free survival, overall survival, and toxicity rate. From September 2013 to July 2018, five patients with MPM were enrolled, and the treatment responses were evaluated. All subjects in this case series were men with a median age of 65 (range, 49–76) years; the mean number of treatment cycles was 3 (range, 2–11). Stable disease was observed in three patients (60%) and progressive disease in two (40%). The median progression-free survival was 2.4 (range, 1.2–11.2) months, and the median overall survival was 9.1 (range, 6.2–22.0) months. Grade 1/2 toxicities, such as nausea and malaise, were reported in all subjects, and most of the toxicities were controllable. Grade 3/4 neutropenia occurred in four patients (80%), and there was no case of febrile neutropenia. Three of our patients achieved stable disease with AMR treatment. These data suggest that AMR is a promising treatment for previously treated MPM in the absence of another treatment. Moreover, AMR is associated with modest toxicities, similar to that in previous reports.

Safety and efficacy of amrubicin monotherapy in patients with platinum-refractory metastatic neuroendocrine carcinoma of the gastrointestinal tract: a single cancer center retrospective study.

PurposePatients with gastrointestinal neuroendocrine carcinoma (GI-NEC) have poor prognoses. Although platinum-based combination chemotherapy is commonly used as first-line treatment, the benefit of amrubicin (AMR) and salvage chemotherapy in those who develop platinum-refractory GI-NEC remains unknown. This study aimed to evaluate the efficacy and safety of AMR monotherapy in patients with platinum-refractory GI-NEC.Patients and methodsPlatinum-refractory GI-NEC patients who received AMR monotherapy between April 2012 and September 2017 were retrospectively analyzed. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. PFS and OS were estimated using Kaplan-Meier methods and compared using log-rank tests.ResultsIn total, 16 patients were enrolled. Of them, 13 (81.3%), 1 (6.2%), and 2 (12.5%) received cisplatin plus irinotecan, cisplatin plus etoposide, and fluoropyrimidine plus platinum, respectively, before AMR monotherapy. The primary sites of NEC included the esophagus (N=3, 18.8%), stomach (N=10, 62.5%), duodenum (N=1, 6.2%) and colorectum (N=2, 12.5%). Patients were administered a median of 3 (range, 1–15) cycles of AMR. The ORR was 6.3%, and the median PFS and OS were 2.9 months (95% CI: 1.7–7.4) and 13.8 months (95% CI: 7.9–23.5), respectively. Neutropenia was the most serious adverse event. Grade 3 or higher neutropenia and febrile neutropenia occurred in 50.0% and 6.2% of patients, respectively. Other nonhematological toxicities were not severe, and no treatment-related deaths occurred. The 10 patients who received subsequent chemotherapy after AMR had significantly longer OS than those who did not (17.3 months vs 8.9 months; p=0.018). The median PFS of those who received organ-specific subsequent chemotherapy after AMR was 3.8 months, which was longer than that of those who received prior AMR.ConclusionAMR is feasible with minimal side effects for platinum-refractory GI-NEC. Organ-specific subsequent chemotherapy after AMR may improve patient survival.

Efficacy of Second-line Chemotherapy in Patients With Sensitive Relapsed Small-cell Lung Cancer.

To evaluate treatment efficacy of cisplatin, etoposide, and irinotecan combined therapy (PEI), platinum-rechallenge chemotherapy (Pt-Re) and amrubicin monotherapy (AMR) for patients with sensitive relapsed small cell lung cancer (SCLC). We defined sensitive relapse as treatment-free interval (TFI) ≥90 days. We retrospectively collected patients' data from medical records between September 2002 and December 2016. Patients with sensitive relapsed SCLC who received second-line chemotherapy were separated into those treated with PEI, with Pt-Re, or with AMR. Seventy-one patients (16 PEI group, 27 Pt-Re group, and 28 AMR group) were assessable for efficacy. No significant differences in patient characteristics were found among the three groups. The median overall survival (MST) was 29.3 months in the PEI group, 24.6 months in the Pt-Re group, and 20.6 months in the AMR group (p=0.042). A significant difference was observed in the overall survival of patients treated with PEI, Pt-Re and AMR and the MST of PEI was the longest.

Efficacy and Safety of Amrubicin in Non-Small-Cell Lung Cancer Patients Beyond Third-Line Therapy

Background: There are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this study was to evaluate the efficacy and safety of amrubicin in pretreated NSCLC patients. Methods: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at Shizuoka General Hospital between April 2007 and March 2015 were retrospectively reviewed. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Results: Overall, 69 patients were enrolled in this study; 16 patients were female and the median age was 67 years. The median number of treatment cycles was 3. The response rate was 7.2%, and the disease control rate was 63.8%. The median progression-free survival was 2.8 months. The median overall survival was 7.7 months. Hematological toxicities of ≥ grade 3 included leukopenia (59.4%) and neutropenia (62.3%). Non-hematological toxicities of ≥ grade 2 included anorexia (27.5%) and fatigue (24.6%). Conclusion: Although hematological toxicities were severe, these results suggested that amrubicin in NSCLC patients beyond third-line therapy shows sufficient clinical benefit.

P1.12-02 Phase II Study of Amrubicin Monotherapy in Elderly or Poor-Risk Patients with Extensive Disease of Small Cell Lung Cancer

Background Previous study indicated that an optional anti-cancer drug for the treatment of small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC). Methods Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m2 amrubicin for 3 consecutive days every 21 days. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results Between March 2011 and August 2015, 36 patients were enrolled in this study. Each patient received a median of four treatment cycles (range, 1–6 cycles). ORR was 52.8% [95% confidence interval (CI), 37–69%]. The median PFS and OS periods were 5.0 months (95% CI, 3.4–6.6 months) and 9.4 months (95% CI, 5.2–13.6 months), respectively. Neutropenia was the most common grade 3 or 4 adverse event (69.4%), with febrile neutropenia developing in 13.9% of patients. No treatment-related death occurred. At the time of starting second-line chemotherapy, 19 of 22 patients (86%) had significantly improved or maintained their performance status (PS) relative to their PS at the time of starting amrubicin monotherapy as first-line chemotherapy (P = 0.027). Conclusions The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC (Clinical trial registration number: UMI11055 www.clinicaltrials.gov).

MS18.02 Treatment of Elderly Patients with SCLC

MS18.02 Treatment of Elderly Patients with SCLC

Amrubicin monotherapy for elderly patients with relapsed extensive-disease small-cell lung cancer: A retrospective study.

BackgroundPrevious studies have shown amrubicin (AMR) to be an effective second‐line treatment option for small‐cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC has not been sufficiently evaluated.MethodsThe medical records of elderly patients with relapsed SCLC who received AMR as second‐line chemotherapy were retrospectively reviewed, and their treatment outcomes were evaluated.ResultsThirty‐one patients with a median age of 72 years (22 patients with sensitive relapse and 9 with refractory relapse) were analyzed. The median number of treatment cycles was four (range: 1–10), and the response rate was 29%. The median progression‐free survival (PFS) and overall survival (OS) were 5.4 and 11.6 months, respectively. The OS of 22 patients who received third‐line chemotherapy was 15.5 months. The PFS (6.2 vs. 3.2 months; P = 0.002) and OS (14.8 vs. 5.7 months; P = 0.004) were significantly longer in patients with sensitive relapse than those with refractory relapse. The frequency of grade 3 or higher neutropenia was high (n = 18, 58%), while febrile neutropenia was only observed in five patients (16%). Non‐hematological toxic effects were relatively mild, and pneumonitis and treatment‐related deaths were not observed.ConclusionAMR may be a feasible and effective regimen for elderly patients with relapsed SCLC.

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.

High expression of topoisomerase-II predicts favorable clinical outcomes in patients with relapsed small cell lung cancers receiving amrubicin

ObjectivesAmrubicin monotherapy is a treatment option for patients with relapsed small cell lung cancers (SCLCs). Topoisomerase-II (Topo-II) – a target of amrubicin – has been reported as a predictive or prognostic marker for chemosensitivity or outcomes in patients with various malignancies. Here, we investigated the prognostic role of Topo-II expression in patients with relapsed SCLCs who underwent amrubicin monotherapy. Materials and methodsEighty-three patients with relapsed SCLCs who received amrubicin monotherapy between 2004 and 2015, after progression beyond first-line chemotherapy, were enrolled in the study. We retrospectively collected clinical data from their medical records, and evaluated the expression levels of Topo-II, by immunohistochemical staining of archival tumor specimens obtained through surgical resections or biopsies. ResultsMost of the enrolled patients were elderly men (89%), with a median age of 70 years (range, 49–83); 16% of these patients showed Topo-II overexpression. Compared to patients with sensitive relapses, those with refractory relapses showed significantly higher Topo-II expression levels (P=0.03). The overall response rates in patients with high and low Topo-II expression were 38.5% and 25.7%, respectively (P=0.34). Multivariate analysis confirmed that patients with a higher Topo-II expression level had significantly longer progression-free survival (hazard ratio (HR), 0.39; P<0.01) and overall survival (HR, 0.48; P=0.04), compared to patients with a lower Topo-II expression level. ConclusionOur study identified Topo-II expression as a significant biomarker for the prediction of favorable outcomes in patients with relapsed SCLCs who underwent treatment with amrubicin, a Topo-II inhibitor. Thus, Topo-II expression may be a promising predictor of the efficacy of amrubicin.

497P - A retrospective study of amrubicin monotherapy for the treatment of relapsed small cell lung cancer in elderly patients

497P - A retrospective study of amrubicin monotherapy for the treatment of relapsed small cell lung cancer in elderly patients