At the 2012 ASCO Annual Meeting, continuation maintenance with paclitaxel and gemcitabine was also reported to benefit MBC patients. In a phase III trial known as KCSG-BR 0702,14
investigators looked at MT with the combination versus observation in MBC patients who had responded to first-line treatment with the two drugs. From the time of randomization to disease progression, patients experienced superior median PFS in the experimental versus the control arm, with a 27% improvement from 3.8 to 7.5 months (P
= .026), and OS rates that were 35% better in the maintenance arm, with a nearly 9-month improvement in survival for patients who continued treatment (P
= .048). The authors of the study suggested the course of treatment for patients with HR-negative, visceral MBC with a high tumor burden.
Alessandra Gennari, of Galliera Hospital in Genoa, Italy, and coauthors provided an overview of the value of maintenance chemotherapy in MBC in 2011.15
In a meta-analysis, Gennari et al evaluated the results of 11 randomized clinical trials that included a total of 2269 patients, with a focus on the duration of first-line chemotherapy regimens and patient outcomes. Some of the regimens involved continuation or switch maintenance. “Longer first-line chemotherapy duration resulted into a marginally longer OS (hazard ratio = 0.91; P
= .046) and a substantially longer PFS (hazard ratio = 0.64; P
<.001),” Gennari et al wrote.
MT in Other Cancers
MT is also being employed in other solid tumor types.
In superficial bladder cancer, maintenance intravesical therapy is standard treatment, according to Smit and Marshall. And in both ovarian and colorectal cancers, they wrote, MT has demonstrated promising results in phase III trials.
Specifically, they said, two phase III trials16,17
tested continuation MT with paclitaxel in ovarian cancer, doubling PFS from 12 to 24 months (P
= .016) and improving OS from 38 to 80 months (P = .012). In colorectal cancer, they wrote, a chemotherapy discontinuation trial used continuation maintenance with leucovorin and fluorouracil, improving PFS from 6.6 to 8.6 months (hazard ratio = 0.61; P
Phase II trials have generated promising results in even more cancer types, including malignant pleural mesothelioma, pancreatic and biliary tree carcinoma, carcinoma of any primary site, head and neck cancer, melanoma, high-grade glioma, and urothelial cancer, Smit and Marshall wrote.
Based on all those results, there’s a growing need for randomized clinical trials of MT, according to Smit and Marshall, with endpoints not just of OS and PFS, but also of quality of life and toxicity.
As such research moves forward, Smit and Marshall added, investigators should help make their studies comparable by adopting specific, universal definitions of MT.
“Although MT is being increasingly investigated in the setting of metastatic solid tumors, it is becoming an established concept only in a few,” they wrote. “With agreement in terminology and with trials designed to specifically evaluate the effect of MT, future trials will be able to better address the role of maintenance therapy in metastatic solid tumors.”
Costs Versus Benefits
With MT playing a growing role in the mix of cancer treatments, both benefits and cost implications can be expected, said Jan. E. Berger, MD, a healthcare consultant and founder of Health Intelligence Partners.
Jan E. Berger, MD
“Value is defined as an equation of quality over cost,” Berger said. “If patients are active, working, bringing money into the national coffers, and paying taxes, the value of long-term treatment is pretty clear. If it’s a matter of going on a chronic medication to give you 4, 6, or 8 months longer of life, that’s the dilemma we’re trying to figure out today in cancer care.”
American health insurance companies, which decide what medical services they are willing to pay for, are likely to support therapies that are recommended in the clinical guidelines of medical advisory associations, such as the NCCN, Berger said. However, she said, the insurers might then compensate for those costs by reconsidering their support of other covered services or products.
Even for patients, decisions about the value of MT can come down to money: how much to spend on expensive medications in the near term versus how much to save for family, Berger said.
In his debate about MT in NSCLC, Goss said that maintenance can come with a “significant” price tag. The incremental cost-effectiveness ratio (ICER) per life-year gained for maintenance pemetrexed in patients with nonsquamous histology, as compared with observation, is $122,371, he said, referring to a study by Klein et al,18
the first to evaluate the cost-effectiveness of MT in advanced NSCLC.