Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies

Okamoto, Isamu; Schuette, Wolfgang; Stinchcombe, Thomas E.; Rodrigues-Pereira, José; Antonio, Belén San; Chen, Jian; Liu, Jingyi; John, William J.; Zinner, Ralph

doi:10.1080/03007995.2017.1297701

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…The safety and toxicity profiles observed for veliparib are consistent with previous studies of veliparib combined with C/PAC in NSCLC [30][31][32]34,42] and in other cancers [33,43]. A limited number of clinical trials have assessed the safety profile of C/PEM in NSCLC, and none in combination with veliparib [44]. Our findings show that the toxicities observed for patients treated with veliparib + nivolumab + C/PEM are similar to those treated with C/PEM and veliparib + C/PAC [31,44], and the toxicity profile of veliparib + nivolumab + C/PEM is consistent with a previous trial of C/PEM combined with pembrolizumab [45,46].…”

Section: Discussionsupporting

confidence: 84%

“…A limited number of clinical trials have assessed the safety profile of C/PEM in NSCLC, and none in combination with veliparib [44]. Our findings show that the toxicities observed for patients treated with veliparib + nivolumab + C/PEM are similar to those treated with C/PEM and veliparib + C/PAC [31,44], and the toxicity profile of veliparib + nivolumab + C/PEM is consistent with a previous trial of C/PEM combined with pembrolizumab [45,46]. Furthermore, patients with nonsquamous NSCLC treated with veliparib + nivolumab + C/PEM in the current study showed similar frequency of hematological toxicities compared with patients receiving C/PEM only in a phase 3 trial [31].…”

Section: Discussionmentioning

confidence: 99%

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Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

et al. 2021

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Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/ metastatic NSCLC. Materials and methods: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL•min, and paclitaxel 200 mg/m 2 (C/ PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/ mL•min, and pemetrexed 500 mg/m 2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed. Results: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range Abbreviations: AUC 0-x , area under the plasma concentration-time curve from time 0 to x hour post dose concentration; AUC t , area under the plasma concentrationtime curve from time 0 to the last measurable concentration; AUC ∞ , area under the plasma concentration-time curve from time 0 to time infinity; AE, adverse event; AUC, target area under the concentration time curve;

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

et al. 2021

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“…Some adverse events after chemotherapy, such as myelosuppression and nausea, were unable to be compared separately. 50 Additionally, we performed subgroup analyses for EGFR 19 del and L858R mutations without other stratified clinical parameters due to incomplete and or immature data. In clinical practice, ethnicity, age, performance status (PS), the presence of brain metastasis, genomic characteristics, concurrent mutations and comorbidities, and patient wishes need to be considered in the decision-making process.…”

Section: Discussionmentioning

confidence: 99%

Pemetrexed/carboplatin plus gefitinib as a first-line treatment for EGFR-mutant advanced nonsmall cell lung cancer: a Bayesian network meta-analysis

et al. 2019

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Background: First-line treatments for nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations have been evaluated in various clinical trials. However, it remains unclear which is the optimal treatment. Methods: A Bayesian network meta-analysis was used to assess the efficacy and safety profile of gefitinib, erlotinib, afatinib, dacomitinib, osimertinib, erlotinib plus bevacizumab and pemetrexed/carboplatin, or pemetrexed alone plus gefitinib. Literature was sourced from electronic databases. Data regarding objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs), treatment-related adverse event grades 3–5 (TRAE 3–5), specific TRAEs [diarrhea, rash, and elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT)] were extracted. The regimens were then ranked using the surface under the cumulative ranking curve (SUCRA). Results: A total of 19 studies involving 4607 EGFR-mutant NSCLC patients were analyzed. In regards to efficacy, pemetrexed/carboplatin (PC) plus gefitinib was superior in ORR and OS to chemotherapy and first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). All the TKI-based regimens had equivalent DCR and PFS. Patients with the L858R mutation treated with PC plus gefitinib achieved a better outcome than most EGFR TKI-related groups (except osimertinib) in the PFS subgroup. In regards to safety, no statistical significance for TRAEs was observed among the eight treatments. In regards to SUCRA, PC plus gefitinib ranked first in terms of PFS, OS, and TRAE grades 3–5. Conclusions: Pemetrexed/carboplatin plus gefitinib is a promising treatment option for EGFR-mutant NSCLC patients in the first-line setting.

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Safety profiles of non-small cell lung cancer patients treated with pemetrexed plus carboplatin: a real-world retrospective, observational, cohort study

Chen

Antonio

Yan

et al. 2017

Current Medical Research and Opinion

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Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies

Cited by 4 publications

References 19 publications

Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

Pemetrexed/carboplatin plus gefitinib as a first-line treatment for EGFR-mutant advanced nonsmall cell lung cancer: a Bayesian network meta-analysis

Safety profiles of non-small cell lung cancer patients treated with pemetrexed plus carboplatin: a real-world retrospective, observational, cohort study

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