Carboplatin–pemetrexed should be ‘a standard option’ for older NSCLC patients
medwireNews: Carboplatin–pemetrexed plus pemetrexed maintenance is noninferior to docetaxel for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) in patients aged 75 years or older, suggests a phase 3 Japanese study.
The combination “provides a clinically significant benefit with regard to its effectiveness and tolerability,” in older patients with nonsquamous disease and “should therefore be considered as a standard option for treatment in this setting,” assert Isamu Okamoto (Kyushu University, Fukuoka) and colleagues.
In total, the trial enrolled 433 patients with stage III–IV or recurrent NSCLC from 79 Japanese institutions between 2013 and 2017.
During the median 17.1-month follow-up, the 216 patients who were randomly assigned to receive four cycles of carboplatin AUC 5 with pemetrexed 500 mg/m2 every 3 weeks, followed by pemetrexed maintenance at the same dose, had a median overall survival (OS) of 18.7 months. By comparison, the median OS of the 217 patients who received docetaxel 60 mg/m2 every 3 weeks was 15.5 months.
Carboplatin–pemetrexed thus achieved a 3.2-month longer OS compared with docetaxel, giving a stratified hazard ratio (HR) of 0.850. As the upper limit of the 95% confidence level fell below the prespecified noninferiority margin of 1.154, the noninferiority of the combination was confirmed, say the researchers.
They were unable to confirm superiority of the combination treatment, however, as the upper limit exceeded the prespecified superiority margin.
Despite this, they report favorable 2-year OS rates of 40.0% with carboplatin–pemetrexed versus 33.4% with docetaxel, and significantly longer progression-free survival, at a median of 6.4 months compared with 4.3 months. Overall response rates were also higher with carboplatin–pemetrexed than docetaxel, at 36.8% versus 28.2%.
The researchers note “[m]arked differences” between cohorts in the incidence of treatment-related adverse events.
Indeed, carboplatin–pemetrexed was associated with higher incidences of grade 3 or 4 anemia (29.5 vs 1.9%) and decreased platelet count (25.6 vs 1.4%) than docetaxel, but with fewer incidences of decreased white blood cell (28.0 vs 68.7%) and neutrophil counts (46.2 vs 86.0%) and febrile neutropenia (4.2 vs 17.7%).
Nevertheless, Okamoto and team stress that “[d]espite the advanced age of the patients enrolled in the present study, treatment-related deaths occurred in only 0.9% of patients in each group.”
And quality of life (QoL) was not impaired with carboplatin–pemetrexed versus docetaxel, with a comparable 29.2% and 28.7% of patients, respectively, reporting improved QoL scores after 18 weeks.
Writing in JAMA Oncology, the study authors conclude: “Collectively, our data thus demonstrate robust effectiveness of carboplatin plus pemetrexed followed by pemetrexed maintenance for first-line therapy of patients with advanced nonsquamous NSCLC 75 years and older.”
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