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Pemetrexed, erlotinib induce similar responses in metastatic NSCLC
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Treatment with pemetrexed or erlotinib induced similar responses in patients with metastatic non–small cell lung cancer that progressed after first- or second-line therapy, according to study results.
Researchers randomly assigned 332 patients to receive pemetrexed (Alimta, Eli Lilly) 500 mg/m2 intravenously once every 3 weeks or erlotinib (Tarceva; Genentech, Astellas Pharma) 150 mg orally once daily. Overall, 23.5% of patients assigned to erlotinib and 21.7% of patients assigned to pemetrexed had squamous cell histology.
Time to tumor progression served as the primary outcome measure.
Researchers reported partial response in 11.4% of patients assigned to pemetrexed (95% CI, 6.6-16.3) vs. 9% of patients assigned to erlotinib (95% CI, 4.7-13.4). Patients in the pemetrexed arm also achieved a higher rate of stable disease (23.5% vs. 17.5%). More patients assigned to erlotinib experienced progressive disease (73.5% vs. 65.1%).
There were no significant differences observed in time to tumor progression (P=.195), ORR (P=.469) or OS (P=.986) between the two arms. However, patients with squamous cell histology who were assigned to erlotinib experienced better time to tumor progression compared with patients assigned to pemetrexed (4.1 months vs. 2.5 months; P=.006).
Incidence of grade 3/4 asthenia, neutropenia and thrombocytopenia were more pronounced in the pemetrexed arm, while the rate of grade 3/4 skin rash was higher in the erlotinib arm.
“The current study failed to meet its primary endpoint, because there was no difference in time to progression between pemetrexed and erlotinib when administered to pretreated patients with advanced/metastatic NSCLC,” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopJoseph Aisner, MD
These data would have been current a few years back. Comparing a tyrosine kinase inhibitor (TKI) to a single-agent chemotherapy empirically and without EGFR mutation data should now be quite passé. Although the authors presented data on testing EGFR mutations, this data was not pivotal in deciding or assigning therapy.
Based on randomized studies, we now know that patients with tumors with certain EGFR mutations have a greater benefit from an EGFR TKI than from chemotherapy, and conversely those whose tumor does not contain these mutations benefit to a greater extent from chemotherapy. Even a small percentage of squamous tumors may benefit from this assessment.
Happily, we are moving away from the empiric guesswork to a more rational decision-making process. Today, rather than randomization between EGFR-directed therapy and chemotherapy, patients would better be assigned to therapy choices based upon the mutational status of the tumor, and the growing list of targets and targeting agents now make this an imperative. Furthermore, the understanding of how EGFR-mutated tumors become resistant to first-line EGFR-directed therapy will both lead to new agents and open the vista for combinatorial therapy.
Given the rapidly evolving data, we are becoming progressively obligated to obtain the genomic mutation information initially — and at the time of disease progression or relapse — to help us give better treatment to patients. To try and do a randomization in the absence of this data is not current therapy. Admittedly, in some instances, getting a tissue sample is very complicated and at best, one can only obtain cytology at times. Most commercial labs will not conduct this data on scanty cytology specimens. Having recognized this, there are now several published reports that suggest this data can be obtained on even small cytology specimens. Given the above, there is an ever-diminishing rationale for using TKI empirically.
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