Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer

Scagliotti, Giorgio Vittorio; Parikh, Purvish; Pawel, Joachim von; Biesma, Bonne; Vansteenkiste, Johan; Manegold, Christian; Serwatowski, Piotr; Gatzemeier, U.; Digumarti, Raghunadharao; Zukin, Mauro; Lee, Jin S.; Mellemgaard, Anders; Park, Keunchil; Patil, Shehkar; Rolski, Janusz; Göksel, Tuncay; Marinis, Filippo de; Simms, Lorinda; Sugarman, Katherine P.; Gandara, David R.

doi:10.1200/jco.2007.15.0375

Cited by 2,899 publications

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“…In a large phase III study of pemetrexed-cisplatin versus gemcitabine-cisplatin, in patients with advanced NSCLC of all histologies (referred to here as "JMDB study"), a pre-specified subgroup analysis in patients with nonsquamous NSCLC showed pemetrexed-cisplatin to have superior survival compared with gemcitabine-cisplatin [5]. This differential efficacy based on histology, as well as a significant treatment-by-histology interaction for pemetrexed, was consistently detected across multiple studies [6].…”

Section: Introductionmentioning

confidence: 92%

“…Detailed descriptions of both trials have been previously published [5], [8] and [9]. In brief, the PARAMOUNT study enrolled 939 chemotherapy-naïve patients primarily from European centers with advanced (stage IIIB or IV) nonsquamous NSCLC to receive four 21-day cycles of pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) induction therapy.…”

Section: Patients and Study Designmentioning

confidence: 99%

“…The JMDB first-line study included 1725 chemotherapy-naïve advanced (stage IIIB or IV) NSCLC patients of any histology [5]. A subset of these patients was identified that matched the key criteria of the patient population of the PARAMOUNT study: nonsquamous NSCLC, treated with at least four 21-day cycles of pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ), without ECOG PS >1 prior to completing the fourth cycle, and without radiologic evidence of disease progression at the time of completing the fourth cycle.…”

Section: Patients and Study Designmentioning

confidence: 99%

“…All analyses were run for the two randomized arms of PARAMOUNT in comparison to the selected homogeneous population from JMDB. Detailed descriptions of the primary statistical analyses of both studies have been previously published [5], [8] and [9]. The following analyses were carried out for the three treatment groups: Kaplan-Meier estimates (including medians) for PFS and OS; Cox hazard ratio estimates [with p-values and 95% confidence intervals (CIs)] for PFS and OS.…”

Section: Statistical Analysesmentioning

confidence: 99%

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Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

et al. 2014

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Highlights•Compared advanced NSCLC phase III trials: pemetrexed-cisplatin with or without pem maintenance.•4 cycles pem-cis followed by pem maintenance improves survival over 6 cycles pem-cis.•Longer exposure to pem-cis or maintenance pem increases some toxicities, but overall incidence low. Abstract ObjectivesTwo phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. MethodsOverall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. ResultsOutcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p = 0.117, HR = 1.16; median OS: 14.0 versus 14.2 months, p = 0.979, HR = 1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p < 0.00001, HR = 0.66; median OS: 16.9 versus 14.2 months, p = 0.003, HR = 0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. ConclusionsThe across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.

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Section: Introductionmentioning

confidence: 92%

Section: Patients and Study Designmentioning

confidence: 99%

Section: Patients and Study Designmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

et al. 2014

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“…A platinum‐based, doublet chemotherapy regimen has been established as standard treatment. Recently, the introduction of pemetrexed has been found to be more effective than gemcitabine as a component of first‐line treatment for patients with non‐squamous carcinoma, particularly adenocarcinoma (median 12.6 vs. 10.9 months) 3, 4…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Zhou

Zuo²,

et al. 2018

Thoracic Cancer

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BackgroundRecombinant human endostatin (rh‐endostatin) plus standard chemotherapy in advanced non‐small cell lung cancer (NSCLC) patients has shown improved efficacy; however, it is unclear whether it is effective and safe when added to pemetrexed/cisplatin and used as maintenance therapy.MethodsWe retrospectively evaluated the data of untreated NSCLC patients administered rh‐endostatin plus pemetrexed/cisplatin or pemetrexed/cisplatin. The primary endpoint was progression‐free survival (PFS).ResultsFifty‐six and 39 patients received rh‐endostatin plus pemetrexed/cisplatin and pemetrexed/cisplatin, and 34 and 29 underwent maintenance treatment, respectively. The median PFS was 10 months (95% confidence interval [CI] 5.85–14.15) in the rh‐endostatin and 8.2 months (4.04–12.36) in the chemotherapy group, but the difference was not statistically significant (P = 0.13). In patients administered maintenance treatment, rh‐endostatin plus pemetrexed was associated with prolonged PFS compared to single‐agent pemetrexed when PFS was calculated from first dosing (13.7 [9.41–17.99] vs. 8.2 [4.16–12.24]; P = 0.032); however, PFS did not differ between the groups (hazard ratio 0.618; 95% CI 0.368–1.038; P = 0.069) after adjusting for clinical factors. No difference was observed in the objective response rate between the groups (48.2% vs. 38.5%; P = 0.346), with the exception of men (62.1% vs. 33.3%; P = 0.032) or in the incidence of drug‐related or grade 3–4 adverse events.ConclusionIn previously untreated, advanced‐stage NSCLC patients, first‐line treatment with pemetrexed/cisplatin plus rh‐endostatin did not prolong PFS or overall survival when compared to pemetrexed/cisplatin, but a trend of improved PFS was observed in patients administered maintenance rh‐endostatin plus pemetrexed.

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Non–Small Cell Lung Cancer and Precision Medicine

Pasche

Grant

2014

JAMA

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Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer

Abstract: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Cited by 2,899 publications

References 30 publications

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Non–Small Cell Lung Cancer and Precision Medicine

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