Regimen confers ‘clinically significant benefit’ for older patients with advanced NSCLC
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First-line treatment with carboplatin plus pemetrexed followed by maintenance pemetrexed appeared noninferior to docetaxel monotherapy in extending OS among older patients with advanced nonsquamous non-small cell lung cancer, according to results of a randomized phase 3 trial published in JAMA Oncology.
The combination also conferred a significant PFS benefit compared with docetaxel alone among this patient population.
“Although the emergence of molecularly targeted agents for oncogene-driven tumors, as well as of immune checkpoint inhibitors, has expanded the opportunity for treatment of advanced [NSCLC] in the elderly, cytotoxic chemotherapy remains the mainstay for the treatment of such patients whose tumors are not driven by known oncogenes or who develop resistance to targeted or immunotherapeutic drugs,” Isamu Okamoto, MD, researcher at the Research Institute for Diseases of the Chest at Kyushu University in Japan, and colleagues wrote. “In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group.”
The JCOG1210/WJOG7813L trial by Okamoto and colleagues included 433 chemotherapy-naive patients aged 75 years and older (median age, 78 years; 57.7% men) with advanced nonsquamous NSCLC across 79 institutions in Japan.
Researchers randomly assigned patients 1:1 to four cycles of carboplatin area under the curve (AUC) 5 plus 500 mg/m² pemetrexed every 3 weeks followed by maintenance pemetrexed at the same dose for 3 weeks (n = 216) or 60 mg/m² docetaxel monotherapy every 3 weeks (n = 217).
OS served as the primary endpoint. Secondary endpoints included PFS, response rate among those with measurable lesions and toxic effects.
Researchers assessed OS on an intention-to-treat basis, and used a stratified Cox regression model to estimate a noninferiority margin of 1.154 for the upper limit of the 95% CI of the HR.
Patients in the docetaxel group received a median four treatment cycles, compared with a median six cycles in the carboplatin-pemetrexed group. More dose reductions occurred in the docetaxel group (61.3% vs. 22.7%).
Median follow-up was 17.1 months.
Researchers observed 167 deaths (77%) among those in the docetaxel group and 161 deaths (74.5%) in the carboplatin-pemetrexed group. Median OS was 18.7 months (95% CI, 16-21.9) in the carboplatin-pemetrexed group compared with 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (stratified HR for OS = 0.85; 95% CI, 0.684-1.056). This confirmed the noninferiority of treatment with carboplatin plus pemetrexed.
Carboplatin plus pemetrexed conferred significantly longer median PFS than docetaxel (6.4 months vs. 4.3 months; unstratified HR = 0.739; 95% CI, 0.609-0.896). Overall response rate did not differ significantly between the carboplatin-pemetrexed and docetaxel groups (36.8% vs. 28.2%).
Patients in the carboplatin-pemetrexed group experienced lower rates of grade 3 or grade 4 leukopenia (28% vs. 68.7%) and neutropenia (46.3% vs. 86%) but higher rates of grade 3 or grade 4 thrombocytopenia (25.7% vs. 1.4%) and anemia (29.4% vs. 1.9%). Common reasons for treatment discontinuation in the docetaxel and carboplatin-pemetrexed groups included disease progression (58.9% vs. 60.7%), adverse events (23.4% vs. 26.2%) and refusal to continue treatment due to toxic effects (13.6% vs. 9.8%).
In the intention-to-treat population, 65% of patients in the docetaxel group (n = 141) and 66.7% of patients in the carboplatin-pemetrexed group (n = 144) received at least one subsequent therapy. Nearly half (48.8%) of those in the docetaxel group received pemetrexed and 37.5% of those in the carboplatin-pemetrexed group received docetaxel.
In addition, 19.8% of patients in the docetaxel group and 25.9% of patients in the carboplatin-pemetrexed group received PD-1 or PD-L1 antibodies, whereas 15.2% and 17.6% received epidermal growth factor receptor tyrosine kinase inhibitors.
The lack of significant differences in OS between the two groups and the lack of cost-effective analysis served as the study’s limitations.
“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance in cytotoxic chemotherapy-naive patients [aged] 75 years and older with advanced nonsquamous NSCLC provides a clinically significant benefit with regard to its effectiveness and tolerability,” the researchers wrote. “This combination should therefore be considered as a standard option for treatment in this setting.” – by Jennifer Southall
Disclosures: Okamoto reports grants/personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan KK, Merck Sharp & Dohme Oncology, Ono Pharmaceutical and Taiho Pharmaceutical; grants from AbbVie, Astellas Pharma and Novartis; and personal fees from Pfizer outside the submitted work. Please see the study for all authors’ relevant financial disclosures.
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