Carboplatin–Pemetrexed ‘Valid Alternative’ For Older Advanced NSCLC Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Carboplatin plus pemetrexed followed by pemetrexed maintenance is a “valid alternative” to docetaxel for older patients with stage III or IV nonsquamous non-small-cell lung cancer (NSCLC), say Japanese investigators. 

Acknowledging interest in the possible use of platinum-based combination regimens for older patients and the favourable tolerability of pemetrexed in NSCLC, Isamu Okamoto, from Kyushu University in Fukuoka, and colleagues designed a noninferiority phase III trial for treatment-naïve patients aged 75 years or older (median 78 years) with a good ECOG performance status.

After a median follow-up of 17.1 months, the team reports a median overall survival (OS) of 18.7 months for the 216 patients who were randomly assigned to receive four 3-week cycles of carboplatin to an AUC of 5 plus pemetrexed 500 mg/m2, followed by a further 3 weeks of pemetrexed treatment.

This compared with a median OS of 15.5 months for the patients who instead were given docetaxel 60 mg/m2 every 3 weeks until disease progression or unacceptable toxicity, giving a hazard ratio (HR) of 0.850 in favour of carboplatin plus pemetrexed.

The upper confidence interval limit was within the prespecified margin for noninferiority of the combination regimen compared with docetaxel, the researchers report in JAMA Oncology, although it did exceed the upper limit for prespecified superiority.

The 2-year OS rates were 40.0% for carboplatin plus pemetrexed and 33.4% for docetaxel. Progression-free survival was significantly longer with the combination regimen, at a median of 6.4 months versus 4.3 months with docetaxel and a HR of 0.739. The corresponding overall response rates were a comparable 36.8% versus 28.2%.

Quality of life assessments conducted at weeks 6, 12 and 18 after trial entry showed that a comparable 29.2% of the carboplatin plus pemetrexed arm and 28.7% of the docetaxel arm showed an improvement in scores from baseline by week 18. 

“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 [aged] 75 years and older”, the investigators summarise.

Isamu Okamoto et al also found “marked differences” for some treatment-related adverse events between the regimens. Treatment with carboplatin plus pemetrexed was associated with higher rates of grade 3–4 anaemia (29.4 vs 1.9%) and thrombocytopenia (25.7 vs 1.4%) than docetaxel, and the “typically high” rates associated with docetaxel were avoided for grade 3–4 neutrophil decreases (46.3 vs 86.0%) and febrile neutropenia (4.2 vs 17.8%).

“Despite the advanced age of the patients enrolled in the present study, treatment-related deaths occurred in only 0.9% of patients in each group”, they comment.

Noting that docetaxel-related febrile neutropenia “is a serious adverse event of cytotoxic chemotherapy that negatively affects survival in patients with advanced NSCLC”, the team concludes: “Given its efficacy and tolerability, the combination of carboplatin and pemetrexed followed by pemetrexed maintenance will be more readily generalizable to daily clinical practice for the first-line treatment of elderly patients with advanced nonsquamous NSCLC.” 

Reference 

Okamoto I, Nokihara H, Nomura S, et al. Comparison of carboplatin plus pemetrexed followed by maintenance pemetrexed with docetaxel monotherapy in elderly patients with advanced nonsquamous non-small cell lung cancer. A phase 3 randomized clinical trial. JAMA Oncol; Advance online publication 12 March 2020. doi:10.1001/jamaoncol.2019.6828