Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial

Paz‐Ares, Luis; Marinis, Filippo de; Dediu, Mircea; Thomas, Michael; Pujol, Jean Louis; Bidoli, Paolo; Molinier, Olivier; Sahoo, Tapan Kumar; Laack, Eckart; Reck, Martin; Corral, J.; Melemed, Symantha; John, William J.; Chouaki, N.; Zimmermann, Annamaria H.; Visseren‐Grul, Carla; Gridelli, Cesare

doi:10.1016/s1470-2045(12)70063-3

Cited by 542 publications

(451 citation statements)

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“…However, the study designs of the abovementioned studies did not allow us to ascertain any benefit of the combination of rh‐endostatin and pemetrexed‐based first‐line chemotherapy and the continued administration of rh‐endostatin after the end of chemotherapy. Pemetrexed‐based first‐line and maintenance chemotherapy is a relatively modern standard regimen for treatment‐naïve, advanced‐stage NSCLC patients, especially for those with the non‐squamous subtype, with a median PFS of 6.9–7.7 months 21, 22. In the current study, the median PFS for patients receiving only first‐line treatment was five months in each group, thus the addition of rh‐endostatin to pemetrexed/cisplatin did not improve PFS ( P = 0.81) during the induction period.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…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%

“…539 patients who completed four cycles of induction therapy with documented radiographic evidence of partial (PR) or complete (CR) tumor response or SD, and who had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, were then randomly assigned (2:1 ratio) to receive maintenance therapy with pemetrexed (500 mg/m 2 ) (n = 359) or placebo (9% sodium chloride) (n = 180). All randomized patients were included in the previously reported efficacy and safety analysis populations [8] and [9] and are included in the analyses described here.…”

Section: Patients and Study Designmentioning

confidence: 99%

“…Of the 378 patients identified, 346 were included in this selected homogeneous patient population used for the analyses here. The other 32 patients were not included because they had been enrolled at Taiwanese or Korean centers, and the PARAMOUNT comparator population did not include patients from those geographic areas [8].…”

Section: Patients and Study Designmentioning

confidence: 99%

“…More recently, the PARAMOUNT study examined pemetrexed continuation maintenance therapy following four cycles of pemetrexed-cisplatin as induction treatment and found significantly improved PFS and OS when administered to non-progressing patients with advanced, nonsquamous NSCLC [8] and [9]. Current guidelines recommend maintenance single-agent pemetrexed for patients with stable disease (SD) or tumor response after four cycles of platinum-containing induction therapy [2], [3] and [4].…”

Section: Introductionmentioning

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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Consolidative Radiotherapy for Limited Metastatic Non–Small-Cell Lung Cancer

et al. 2018

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Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial

Cited by 542 publications

References 23 publications

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

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

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

Consolidative Radiotherapy for Limited Metastatic Non–Small-Cell Lung Cancer

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