Untreated Extensive Small-cell Lung Cancer Research Articles

First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China.

IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. The aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay (WTP) threshold were performed to identify the uncertain parameters of Markov model. Total costs of atezolizumab group were $48,129, while cost of chemotherapy alone was just $12,920 in placebo group. The quality-adjusted life-years (QALYs) in atezolizumab group was just 0.072 higher than that in placebo group (0.858 QALYs vs. 0.786 QALYs). The cost-effectiveness ratio between atezolizumab combination with chemotherapy and chemotherapy alone was $489,013/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the progression-free survival (PFS) and progression disease state in placebo group were the most influential parameter. Atezolizumab combination therapy was not more cost-effective than chemotherapy alone at a WTP threshold of $25,929/QALY in China.

Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive small cell lung cancer in China.

e20083 Background: Atezolizumab plus chemotherapy as a first-line therapy has shown significant survival benefits in patients with extensive small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. Here, the aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. Methods: A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay threshold (WTP) were performed to identify the uncertain parameters of Markov model. Results: Total costs of atezolizumab group was $183801, while cost of chemotherapy alone group was just $12920 in placebo group. The QLAYs in atezolizumab group was just 1.15 higher than that in placebo group (13.73 QALYs vs. 12.58 QALYs). The ICER between atezolizumab combination with chemotherapy and chemotherapy alone was $148592/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the PFS and PD state in placebo group were the most influential parameter. Conclusions: Atezolizumab combination therapy was not more cost-effective than chemotherapy alone therapy at a WTP threshold of $25929/QALYs in China.

Randomized phase II–III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial

This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: Results from the IFCT-0802 trial.

7505 Background: A randomized phase II-III trial was designed to assess efficacy and safety of adding bevacizumab (Bev) to first-line standard chemotherapy (CT) in extensive small-cell lung cancer ...

Result of phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small cell lung cancer.

7507 Background: Etoposide combined with cisplatin (EP) has been the first-line chemotherapy regimen for small cell lung cancer (SCLC) for >20 years; however, a more effective regimen has been recommended by many clinical oncologists. Thus, we here present our preliminary results of a phase III clinical trial of the novel drug amrubicin in combination with cisplatin (AP) in comparison to EP in patients with previously untreated extensive SCLC (ED-SCLC). Methods: A total of 299 previously untreated ED-SCLC patients were randomized (ratio, 1:1) into two treatment groups: (1) the AP group (n = 149): 4–6 cycles of amrubicin (40 mg/m2/day on days 1–3) and cisplatin (60 mg/m2/day on day 1) and (2) the EP group (n = 150): 4–6 cycles of etoposide (100 mg/m2/day on days 1–3) and cisplatin (80 mg/m2/day on day 1 every 21 days). Patients were evaluated for therapy response and electrocardiography results every 2 cycles. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and general safety. Results: Baseline characteristics were similar among the two groups. For AP and EP groups, the median OS was 11.79 and 10.28 months, the median PFS was 7.13 and 6.37 months, and ORR was 69.8% and 57.3%, respectively. The most frequent adverse events (≥grade 3) in AP and EP groups were bone marrow failure (23.5% and 21.3%, respectively), neutropenia (54.4% and 44.0%, respectively), and leukopenia (34.9% and 19.3%, respectively). Conclusions: Our phase III trial demonstrated that for previously untreated ED-SCLC patients, AP therapy was not inferior to EP therapy in terms of OS and offered predictable and manageable toxicities. Clinical trial information: NCT00660504.

Randomized Phase III Intergroup Trial of Etoposide and Cisplatin With or Without Paclitaxel and Granulocyte Colony-Stimulating Factor in Patients With Extensive-Stage Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 9732

To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. Eligible patients (N=587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.

Preliminary results of a phase II study of irinotecan and etoposide combination as first line chemotherapy for extensive small-cell lung cancer

7366 Background: The purpose of this study is to evaluate the antitumor activity and toxicity of a new combination of irinotecan and etoposide for previously untreated extensive small-cell lung cancer (E-SCLC). Methods: 23 patients of 30 expected are included in the study. 17 are male and 6- female with a median age of 64 (46–79 years). 15 patients were at metastatic stage and 7 were locally advanced. The chemotherapy combination included irinotecan 60–80 mg/m2 day 1,8, 15, and etoposide 80 mg/ m2 days 1–3, every 4 weeks for 6 cycles. Evaluation is made every second cycle. Colony stimulating factors are allowed. Results: Among the 23 patients included 3 are under treatment and not yet evaluable. 13 (62%) showed an objective response with 5 (24%) complete responses, 3 (14%) stable disease and 5 (24%) progressive disease. Incidences of grade III-IV febrile and non-febrile neutropenia were 7, 7. Diarrhea was observed in 7% of all courses. Grade III-IV nausea and vomiting occurs in 3(14%) patients. No treatment-related death was observed. Conclusion: The combination of irinotecan and etoposide shows a promising objective response rate with a well-tolerated toxicity in patients with E-SCLC. Detailed results will be presented after longer follow-up. No significant financial relationships to disclose.

Preliminary results of a phase II study of irinotecan and etoposide combination as first line chemotherapy for extensive small-cell lung cancer

7366 Background: The purpose of this study is to evaluate the antitumor activity and toxicity of a new combination of irinotecan and etoposide for previously untreated extensive small-cell lung cancer (E-SCLC). Methods: 23 patients of 30 expected are included in the study. 17 are male and 6- female with a median age of 64 (46–79 years). 15 patients were at metastatic stage and 7 were locally advanced. The chemotherapy combination included irinotecan 60–80 mg/m2 day 1,8, 15, and etoposide 80 mg/ m2 days 1–3, every 4 weeks for 6 cycles. Evaluation is made every second cycle. Colony stimulating factors are allowed. Results: Among the 23 patients included 3 are under treatment and not yet evaluable. 13 (62%) showed an objective response with 5 (24%) complete responses, 3 (14%) stable disease and 5 (24%) progressive disease. Incidences of grade III-IV febrile and non-febrile neutropenia were 7, 7. Diarrhea was observed in 7% of all courses. Grade III-IV nausea and vomiting occurs in 3(14%) patients. No treatment-related death was observed. Conclusion: The combination of irinotecan and etoposide shows a promising objective response rate with a well-tolerated toxicity in patients with E-SCLC. Detailed results will be presented after longer follow-up. No significant financial relationships to disclose.

Phase I/II Trial of Etoposide and Carboplatin in Extensive Small-Cell Lung Cancer

Previously untreated extensive small-cell lung cancer (SCLC) patients with performance status 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and carboplatin doses of 50, 100, or 125 mg/m2/day on days 1-3 in a Phase I format. Among the ten eligible patients treated with 125 mg/m2/day of carboplatin, grade 3 or 4 infection occurred in six patients, grade 4 thrombocytopenia in four patients, and there was one death with myelosuppression. Thus, this dose was considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted utilizing this treatment program. In the Phase II trials, 81% of the 48 eligible patients had grade 3 or 4 leukopenia, 76% had grade 3 or 4 thrombocytopenia, and 55% had grade 3 or 4 anemia. There were three (6%) toxic deaths from myelosuppression. The objective response rate was 63% (17% complete responders) with a median response duration of 6.2 months for complete responders and 6.4 months for partial responders. Median survival was 12 months. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 25% increase in carboplatin compared to prior studies. Cancer and Leukemia Group B (CALGB) plans to study further dose intensification of this regimen with colony-stimulating factors.

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.