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Newer NSCLC treatments confer modest increase in survival at high cost
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Therapies introduced in the mid-2000s to treat advanced-stage non–small cell lung cancer — including pemetrexed, erlotinib and bevacizumab — are associated with a 1.5-month survival increase and approximately an $8,000 increase in outpatient spending per patient, according to a 12-year study published in Journal of Clinical Oncology.
Researchers compared the costs and efficacy of pemetrexed (Alimta, Eli Lilly), erlotinib (Tarceva; Genentech, Astellas Oncology) and bevacizumab (Avastin, Genentech) with three of the drugs they replaced — paclitaxel, gemcitabine and vinorelbine.
“As new therapies were introduced, they were rapidly adopted and the old therapies were abandoned,” Cathy Bradley, PhD, associate director for population sciences research at University of Colorado Cancer Center, said in a press release. “Across the population in the past 12 years, these newly approved therapies have made little difference in OS.”
NSCLC is the leading cause of cancer death in the United States and has a 5-year relative survival rate of 4.2%. Pemetrexed was first approved by the FDA in 2004 for malignant pleural mesothelioma and again in 2009 as maintenance therapy for nonsquamous NSCLC. The FDA approved erlotinib as a maintenance therapy in 2004. Bevacizumab was first approved in 2004 for metastatic colorectal cancer and in 2006 received FDA approval with chemotherapy in treatment of most common–type lung cancers.
Researchers used SEER–Medicare data on 22,163 patients aged 65 years or older newly diagnosed with advanced-stage NSCLC who were treated with antineoplastic agents between 2000 and 2011. Researchers evaluated days on each treatment, survival and medical costs in the 12 months after diagnosis.
From 2000 to 2011, researchers observed a rapid increase in the use of pemetrexed (39.2%), erlotinib (20.3%) and bevacizumab (18.9%), and a decline in paclitaxel (38.7%), gemcitabine (17%) and vinorelbine (5.7%, all P < .05).
The average total days on newly introduced therapy increased by 5 days (103 to 108); patients who received pemetrexed, erlotinib or bevacizumab had the longest average treatment durations (approximately 146 days vs. 75 days for other agents).
In the last 30 days of life, 44% of patients received chemotherapy or a targeted agent.
Bradley said many of the targeted therapies are only useful when directed at a cancer with a specific biomarker.
“Take erlotinib,” she said. “A patient’s tumor must be marked by EFGR for it to be beneficial. But when some patients reach the end of their established options, some oncologists may prescribe erlotinib without the EFGR biomarker in hopes that the patient will benefit.”
Acute inpatient spending declined from $29,376 in 2000 to $23,731 in 2011 (approximately $5,600 per person), whereas outpatient spending increased 23%, from $37,931 in 2000 to $46,642 in 2011 (approximately $8,700 per person). Medial survival gain was approximately 1.5 months, from 7.7 months in 2000 to 9.2 in 2010 (P < .001).
Patients with cancer are 2.5 times more likely to declare bankruptcy than those who do not, and that out-of-pocket treatments often range between $30,000 and $40,000, according to the press release.
“When you talk with patients, leaving their family in financial distress is an important concern,” Bradley said. “What we see here doesn’t definitely mean these drugs are unsuccessful. It means that despite their promise in clinical trials, they haven’t made a survival difference in the population. That may be because oncologists are giving them to people who will not benefit. Better predicting who will benefit from newer, more expensive therapies is essential to making value-based decisions m the context of very high costs and new medicines.” – by Chuck Gormley
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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For those who practiced oncology between 2000 and 2011 — the period studied by Bradley and colleagues — the 1.5-month increase in median survival among patients with advanced non–small cell lung cancer aged older than 65 years who received systemic antineoplastic therapy is sobering but not surprising.
Despite incremental — and what were felt to be meaningful — advances in survival shown in phase 3 trials with agents such as pemetrexed (Alimta, Eli Lilly), bevacizumab (Avastin, Genentech) and erlotinib (Tarceva, Genentech) when used in unselected patients, the fact remains that most patients do not experience sustained benefit from these expensive drugs.
Targeted agents were only beginning to be more widely — and wisely — used for patients with EGFR and ALK alterations by the end of 2011, so their impact is not truly shown here, albeit in what is a small percentage of the total population with advanced NSCLC.
The researchers’ linkage of Medicare claims data to outcomes data from the SEER registry provides useful perspective regarding the contribution of drug costs to total expenditures for patients with advanced cancer. Inpatient care accounts for the largest proportion of payments; thus, hospitalization costs and quality have been a major focus of CMS’ efforts to control spending. This is reflected in the somewhat mild rise in payments during the period studied, despite the relatively rapid adoption of more expensive chemotherapy drugs. However, CMS programs — such as the Merit-based Incentive Payment System and the Oncology Care Model — are newly minted efforts to address outpatient quality metrics and costs. Thus, value-based decision-making soon will become a large part of what we do in practice.
The excitement surrounding the entry of immunotherapeutics into the treatment paradigm for advanced NSCLC has been contagious, and we see individual patients who truly have remarkable responses to PD-1 and PD-L1 inhibitors. But will a similar analysis over the second decade of this century again prove disappointing? Should our goals in drug development and clinical trial design continue to be achieved in such small steps, or is a moonshot possible?
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