Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer
Abstract
PURPOSE: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS: Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P <or= .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. CONCLUSION: 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.
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Platinum-based double-agent chemotherapy was the existing standard of care for newly diagnosed advanced ALK-positive NSCLC.
“as compared with the existing standard-of-care, platinum-based double-agent chemotherapy, 11,12 is unknown.”
From First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer (2014) · cites this paper as [12]
Pemetrexed-based combination chemotherapy shows a slight but significant survival benefit compared with gemcitabine- or docetaxel-based combinations.
“Pemetrexed-based combination chemotherapy represents a therapeutic option, based on the results of a recent meta-analysis that showed a slight but significant survival benefit compared with gemcitabine-or docetaxel-based combinations and of a pre-planned subgroup analysis of a large randomised phase III trial [II, A] [54, 55].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [55]
The results of the Scagliotti et al trial suggest that a platinum agent plus pemetrexed should not be administered in patients with SCC.
“The results of this trial suggest that a platinum agent plus pemetrexed should not be administered in patients with SCC, and in fact, licensing in many health care jurisdictions limits the use of pemetrexed for patients with nonsquamous histology.”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [68]
The trial by Scagliotti et al comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed demonstrated improved OS for patients with SCC treated with cisplatin plus gemcitabine.
“The trial by Scagliotti et al68 comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed demonstrated improved OS for patients with SCC treated with cisplatin plus gemcitabine.”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [68]
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- Authors
- Scagliotti, G. V., Parikh, P., von Pawel, J., Biesma, B., Vansteenkiste, J., Manegold, C., Serwatowski, P., Gatzemeier, U., Digumarti, R., Zukin, M., Lee, J. S., Mellemgaard, A., Park, K., Patil, S., Rolski, J., Goksel, T., de Marinis, F., Simms, L., Sugarman, K. P., & Gandara, D.
- Affiliations
- Nizam's Institute of Medical Sciences (IN)
- From the University of Torino, Orbassano; San Camillo-Forlanini Hospitals, Rome, Italy; Tata Memorial Hospital, Mumbai; Nizam's Institute of Medical Sciences, Hyderabad; Bangalore Institute of Oncology, Bangalore, India; Asklepios-Fachkliniken Munchen, Gauting; Heidelberg University Medical Center, Mannheim; Hospital Grosshansdorf, Grosshansdorf, Germany; Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, the Netherlands; University Hospital Gasthuisberg, Leuven, Belgium; Specjalistyczny Szpital Im, Szczecin;...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2008-07-20
- Volume
- 26
- Issue
- 21
- Pages
- 3543-3551
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2099725888
- Cited by
- 3,203
- References
- 2
- Citations by year
- 2026: 40 · 2025: 39 · 2024: 75 · 2023: 69 · 2022: 89 · 2021: 147 · 2020: 164 · 2019: 161 · 2018: 198 · 2017: 217 · 2016: 201 · 2015: 245 · 2014: 268 · 2013: 298 · 2012: 265
- FWCI
- 222.09
- Type
- journal article
- Language
- en
- Update notices
- new_edition (2023-05-05)
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, cisplatin, gemcitabine, pemetrexed, first-line chemotherapy, non-inferiority, overall survival, advanced lung cancer, adenocarcinoma, squamous cell carcinoma, large cell carcinoma, neutropenia, febrile neutropenia, treatment toxicity, platinum-based regimens
- MeSH terms
- Pemetrexed, Gemcitabine, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Cisplatin, Deoxycytidine, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Kaplan-Meier Estimate
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