Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy

Author(s): Nasser Hanna, Frances A. Shepherd, Frank V. Fossella, Jose R. Pereira, Filippo De Marinis, Joachim von Pawel, Ulrich Gatzemeier, Thomas Chang Yao Tsao, Miklos Pless, Thomas Muller, Hong-Liang Lim, Christopher Desch, Klara Szondy, Radj Gervais, Shaharyar, Christian Manegold, Sofia Paul, Paolo Paoletti, Lawrence Einhorn, and Paul A. Bunn Jr.
Source: DOI: 10.1200/JCO.22.02546 Journal of Clinical Oncology 41, no. 15 (May 20, 2023) 2682-2690.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Throwback by JCO! Docetaxel vs Pemetrexed in 2L NSCLC showed similar OS/PFS outcomes, but Pemetrexed was tolerated better particularly in terms of myelosuppression. Pemetrexed was active in squamous cancers as well.


To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.


Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m2 intravenously (IV) day 1 with vitamin B12, folic acid, and dexamethasone or docetaxel 75 mg/m2 IV day 1 with dexamethasone every 21 days. The primary end point was overall survival.


Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P = .105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P < .001), febrile neutropenia (12.7% v 1.9%; P < .001), neutropenia with infections (3.3% v 0.0%; P = .004), hospitalizations for neutropenic fever (13.4% v 1.5%; P < .001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P = .092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P < .001) and all grade alopecia (37.7% v 6.4%; P < .001) compared with patients receiving pemetrexed.


Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.

Author Affiliations

From Indiana University and the Hoosier Oncology Group; Eli Lilly and Company, Indianapolis, IN; The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of Colorado Cancer Center, Denver, CO; Virginia Cancer Institute, Richmond, VA; Princess Margaret Hospital and the University of Toronto, Toronto, Ontario, Canada; Instituto Arnaldo Vieira de Carvalho, Sao Paolo, Brazil; San Camillo-Forlanini Hospitals, Rome, Italy; Chang Gung Memorial Hospital, Taoyuan, Taiwan; University Hospital Basel, Petersgraben Switzerland; Fachklinik München, Gauting; Hospital Grosshansdorf, Grosshansdorf; Krankenhaus Hofheim Am Taunus, Hofheim; Thoraxklinik-Heidelberg, Heidelberg, Germany; National University Hospital, Singapore; Semmelweis Medical University Diosarok, Budapest, Hungary; Centre Francois Baclesse, Caen, France; Mayo Hospital, Lahore, Pakistan.

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