Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer

Our plain-English summary of Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer, by S. Ricciardi, S. Tomao, F. de Marinis (Therapeutics and Clinical Risk Management, 2009).

The study

• Authors: S. Ricciardi, S. Tomao, F. de Marinis
• Journal: Therapeutics and Clinical Risk Management
• Published: 2009;5:781-7
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pemetrexed is a new cytotoxic agent that is a standard of care for the second-line treatment of non-small cell lung cancer (NSCLC) and in combination with cisplatin in treatment of malignat pleural mesothelioma. It has been studied in numerous phase II and III trials in combination with different drugs or as single agent. Recently, pemetrexed has been approved in combination with cisplatin for the first-line treatment of patients with locally advanced or metastatic NSCLC other than squamous cell histology. The toxicity is acceptable and similar to that of other NSCLC regimens. The postinduction maintenance therapy with pemetrexed is being evaluated in a phase III, double-blind, placebo-controlled study.

In plain English

This was a review article, not a new study. The authors, based in Rome, described published phase II and phase III trials of the chemotherapy drug pemetrexed in non-small cell lung cancer (NSCLC). Asbestos appeared only in the introduction, as one of several occupational and environmental substances that may increase lung cancer risk. The review also described the trial behind the drug's 2003 FDA approval for malignant pleural mesothelioma. In that trial of 448 patients, the overall response rate was 41.3% with pemetrexed plus cisplatin and 16.7% with cisplatin alone. In a reviewed phase III trial of 1725 previously untreated NSCLC patients, 12-month survival was 43.5% with cisplatin/pemetrexed and 41.9% with cisplatin/gemcitabine. Among patients with adenocarcinoma in that trial, median survival was 12.55 months with cisplatin/pemetrexed and 10.94 months with cisplatin/gemcitabine. A reviewed maintenance trial reported progression-free survival of 4.3 months with pemetrexed and 2.6 months with placebo. The authors concluded that pemetrexed is active against advanced or metastatic NSCLC in first- and second-line treatment. They saw potential for it in tumors other than predominantly squamous cell histology.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published clinical trials (no new data collected by the authors)
• Who was studied: No study population of its own. The authors reviewed published phase II and III trials of pemetrexed in patients with NSCLC, plus one phase III trial in malignant pleural mesothelioma.
• Exposure: The exposure was treatment with the chemotherapy drug pemetrexed, alone or combined with other drugs. Asbestos exposure was not studied; it was mentioned only as one background risk factor for lung cancer.
• Main results:
  • In the reviewed malignant pleural mesothelioma trial (448 patients, cisplatin plus pemetrexed vs cisplatin alone), the overall response rate was 41.3% in the pemetrexed/cisplatin arm and 16.7% in the cisplatin-alone arm. Survival was reported as improved by 3 months.
  • In the reviewed Scagliotti phase III trial (1725 chemotherapy-naive patients with advanced NSCLC), 12-month survival was 43.5% with cisplatin/pemetrexed and 41.9% with cisplatin/gemcitabine. Overall survival with cisplatin/pemetrexed was reported as non-inferior.
  • In the same reviewed trial, patients with adenocarcinoma had a median survival of 12.55 months with cisplatin/pemetrexed and 10.94 months with cisplatin/gemcitabine. Patients with large cell carcinoma had 10.38 months and 6.67 months respectively.
  • In the same reviewed trial, grade 3–4 neutropenia occurred in 15% of patients given pemetrexed and in 27% of patients given cisplatin/gemcitabine.
  • In the reviewed Ciuleanu maintenance trial (pemetrexed given after initial chemotherapy, compared with placebo), progression-free survival was 4.3 months with pemetrexed and 2.6 months without it (hazard ratio 0.502, 95% confidence interval 0.41 to 0.61).
• The authors' conclusion: The authors concluded that pemetrexed is active against advanced or metastatic NSCLC as both first- and second-line treatment. They wrote that it has potential in tumors other than predominantly squamous cell histology.

Topics

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), First-line Therapy, Non-Small Cell Lung Cancer, Cisplatin, Pleural Mesothelioma, Squamous Cell Carcinoma, Histology.

Related studies

• Pemetrexed as second-line therapy for advanced non-small-cell lung cancer (NSCLC) — E. Felip, R. Rosell (2008)
• Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2013)
• Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review — X.Q. Jing, L. Zhou, et al. (2016)
• PD-L1 pfeRNAs as blood-based predictors of treatment response of unresectable malignant pleural mesothelioma patients administered Durvalumab with cisplatin and pemetrexed as first-line therapy — A. Gurau, S. Yamauchi, et al. (2025)
• Haematological toxicity of pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung with third-space fluid — W.C. Kwok, T.F. Cheong, et al. (2021)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)

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