Dataset Information

Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan.

ABSTRACT:

Background

A previous study showed a survival benefit with maintenance therapy with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether continuation maintenance therapy with pemetrexed is beneficial in Japanese patients. Here, we present our phase II study that assessed the efficacy and safety of cisplatin plus pemetrexed as induction chemotherapy, followed by maintenance therapy with pemetrexed in advanced NSCLC patients in Japan.

Methods

Chemotherapy-naïve patients received 500?mg/m(2) pemetrexed and 75?mg/m(2) cisplatin on day one every three weeks for four cycles. In patients who responded to therapy or achieved stable disease, pemetrexed was continued until disease progression. The primary endpoint of this study was the progression-free survival rate at six months (PFS-6).

Results

Of the 35 patients initially enrolled in the study, 18 (51%) received maintenance chemotherapy with pemetrexed. The median PFS was 6.7 months, and the PFS-6 was 60% (95% confidence interval [CI], 42-76%). Median overall survival (OS) was 15.5 months (95% CI, 8.3-22.7 months). The median PFS and OS in patients who received maintenance chemotherapy with pemetrexed were 9.5 months and 25.3 months, respectively. The most frequently noted severe toxicity during induction chemotherapy was neutropenia, which occurred in seven patients. Two patients discontinued maintenance therapy owing to prolonged grade 2 edema in one patient and grade 3 neutropenia in another.

Conclusion

Continuation maintenance chemotherapy with pemetrexed is associated with a survival benefit in patients who have completed induction chemotherapy for non-squamous NSCLC.

SUBMITTER: Asami K

PROVIDER: S-EPMC4704346 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan.

Asami Kazuhiro K Kawahara Masaaki M Hirashima Tomonori T Suzuki Hidekazu H Okishio Kyoichi K Omachi Naoki N Tamiya Motohiro M Tamiya Akihiro A Hirooka Aya A Nakao Keiko K Tsuji Taisuke T Atagi Shinji S

Thoracic cancer 20140703 4

<h4>Background</h4>A previous study showed a survival benefit with maintenance therapy with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether continuation maintenance therapy with pemetrexed is beneficial in Japanese patients. Here, we present our phase II study that assessed the efficacy and safety of cisplatin plus pemetrexed as induction chemotherapy, followed by maintenance therapy with pemetrexed in advanced NSCLC patients in Japan. ...[more]

PMID: 26767015

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Project description:BackgroundMaintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research.MethodsThis multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs).ResultsA total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the induction and continuation maintenance therapies were generally well-tolerated, and similar proportion of patients in each arm experienced at least 1 grade 3/4 TEAE (pemetrexed/BSC, 17.9%; BSC, 18.5%).ConclusionsContinuation pemetrexed maintenance therapy resulted in promising PFS with an acceptable safety profile in a Middle Eastern population with advanced non-squamous NSCLC and is worthy of further investigation.Trial registrationNCT00606021.

Project description:BackgroundPembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.MethodsCAP29 is a retrospective, observational, multicenter real-life study conducted in 6 French centers. We evaluated efficacy of first-line setting chemotherapy plus pembrolizumab (November 2019 to September 2020) in advanced (stage III-IV) non-squamous non-small cell lung cancer patients without targetable alterations. Primary endpoint was progression-free survival. Secondary endpoints were overall survival, objective response rate and safety.ResultsWith a median follow-up of 4.5 months (0 to 22 months), a total of 121 patients were included. Baseline characteristics were: median age of 59.8 years with 7.4% ≥75 years, 58.7% of males, 91.8% PS 0-1, 87.6% of stage IV with ≥3 metastatic sites in 62% of cases. Patients had brain and liver metastases in 24% and 15.7% of cases, respectively. PD-L1 was <1% (44.6%), 1-49% (28.1%) and ≥50% (21.5%). Median progression-free survival and overall survival achieved 9 and 20.6 months, respectively. Objective response rate was 63.7% with 7 prolonged complete responses. Survival benefit seemed to be correlated with PD-L1 expression. Brain and liver metastases were not statistically associated with decreased overall survival. Most common adverse events were asthenia (76%), anemia (61.2%), nausea (53.7%), decreased appetite (37.2%) and liver cytolysis (34.7%). Renal and hepatic disorders were the main causes of pemetrexed discontinuation. Grade 3-4 adverse events concerned 17.5% of patients. Two treatment-related deaths were reported.ConclusionsFirst-line pembrolizumab plus chemotherapy confirmed real-life efficacy for patients with advanced non-squamous non-small cell lung cancer. With median progression-free survival and overall survival of 9.0 and 20.6 months, respectively and no new safety signal, our real-life data are very close to results provided by clinical trials, confirming the benefit and the manageable toxicity profile of this combination.

Project description:Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting.Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0-1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m(2) every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients' quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011.This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design requires unusual methodology and specific logistics to address outcomes relevant to the home-delivery approach. This article presents a study design that offers a novel and reproducible model for home-based chemotherapy, and provides an up-to-date overview of the literature regarding this type of treatment.ClinicalTrials.gov: NCT01473563.

Project description:ImportanceFew clinical trials have been specifically designed for elderly patients with advanced non-small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit.ObjectiveTo determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC.Design, setting, and participantsThis open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy-naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019.InterventionsPatients were randomized to receive either docetaxel monotherapy (60 mg/m2) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m2) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks.Main outcomes and measuresThe primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model.ResultsOf the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n?=?217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n?=?216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority?=?.003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed.Conclusion and relevanceCarboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460.

Dataset Information

Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan.

Background

Methods

Results

Conclusion

Publications

Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan.

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