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Cisplatin fails to improve survival for elderly patients with lung cancer

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August 10, 2018

The addition of cisplatin to single-agent chemotherapy did not significantly improve OS or quality-of-life scores among elderly patients with advanced non-small cell lung cancer, according to a combined analysis of two parallel phase 3 trials.

However, the addition of cisplatin did improve PFS and objective response rate.

“More than one-third of lung cancer cases are diagnosed in patients older than age 70 years, and the majority of elderly patients have metastatic disease at the time of diagnosis,” Cesare Gridelli, MD, chief of division of medical oncology at the S.G. Moscati Hospital in Italy and colleagues wrote.

“Even in the era of precision medicine — excluding 15% to 20% of patients with an epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-positive tumor and another 25% to 30% with a programmed death-ligand 1(PD-L1)-positive tumor — a combination chemotherapy that includes cisplatin remains the standard treatment for the majority of adult patients with advanced NSCLC,” they added. “However, there are concerns about the tolerability and feasibility of using cisplatin for elderly patients who might have an increased risk of life-threatening toxicity.”

Gridelli and colleagues assessed 531 patients (median age, 75 years; 79% men; 70% nonsquamous histology) with advanced NSCLC aged 70 years or older and an ECOG performance status of 0 to 1 from the MILES-3 and MILES-4 trials. Researchers randomly assigned patients to gemcitabine or pemetrexed with (n = 263) or without (n = 268) cisplatin.

After a median follow-up of 2 years, researchers observed 384 deaths and 448 PFS events.

Among those randomly assigned cisplatin, researchers observed improved PFS (HR = 0.76; 95% CI, 0.63-0.92) and greater objective response rate (15.5% vs. 8.5%; P = .02) compared with those assigned single-agent chemotherapy alone.

However, those randomly assigned cisplatin did not have significantly prolonged OS (HR = 0.86; 95% CI, 0.7-1.05) compared with those treated with a cisplatin-free regimen. Researchers observed a median OS of 7.5 months (95% CI, 6.2-9.5) in the monotherapy arm compared with 9.6 months (95% CI, 8.1-11.7) in the cisplatin arm.

Researchers observed an improvement of at least 10 points in quality of life among 39.3% of patients assigned single-agent chemotherapy compared with 37.2% of those assigned cisplatin, which did not represent a significant difference.

Cisplatin was associated with more adverse events, including hematologic and neurologic toxicity, mucositis, nausea, vomiting, severe thrombocytopenia, leucopenia, neutropenia, febrile neutropenia, fatigue and anorexia.

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The main limitation of the study included slow enrollment, which led researchers to combine the MILES-3 and MILES-4 trials.

In remains a question when to offer new treatments — including platinum doublets with or without antiangiogenics and immune checkpoint inhibitors — and molecularly targeted tyrosine kinase inhibitors to older and younger patients, Paul A. Bunn Jr., MD, and Anastasios Dimou, MD, of University of Colorado Denver and University of Colorado Cancer Center, wrote in an accompanying editorial.

“The question cannot have a universal answer because of the heterogeneity of clinical features among the elderly, which are not universally controlled for in clinical trials,” they wrote. “However, results indicate that most fit elderly patients with performance status of 0 to 1 may be offered carboplatin-based doublets with or without checkpoint inhibitor antibodies, checkpoint inhibitor antibodies alone or molecularly targeted TKIs,” they wrote. “Ultimately, physicians need to use their judgment and include patient informed preference and quality of life in addition to survival endpoints in decision-making.” – by Cassie Homer

Disclosures: Gridelli reports consultant/advisory roles with Bristol-Myers Squibb and Merck Oncology; speakers bureau roles with Bristol-Myers Squibb, Genentech and Merck Oncology; and research funding from Eli Lilly. Please see the study for all other authors’ relevant financial disclosures. Bunn reports consultant/advisory roles with AbbVie, AstraZeneca/MedImmune, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, Merck Serono and Novartis. Dimou reports no relevant financial disclosures.