What Is the Role of Maintenance Therapy in Cancer Care?

Beth Fand Incollingo @fandincollingo | May 01, 2013
“We use maintenance therapy as part of standard practice, but we haven’t done many trials to say when to optimally introduce it or when to use new drugs, and it’s still controversial at what point we discontinue any of the therapies,” he said. “Furthermore, we don’t really have drugs that we use purely in the maintenance therapy setting, other than the biological drugs. Determining when to use maintenance therapy still remains part of the art of oncology. You have to use your common sense as best you can, and use the data we have to decide when and how and in what situation to use maintenance therapy.”

The particulars of MT are more defined in nonsquamous NSCLC. In patients with advanced NSCLC who have stable disease, good performance status, and other favorable factors, MT should be given after 4 to 6 cycles of first-line chemotherapy, according to the National Comprehensive Cancer Network’s (NCCN’s) 2013 Clinical Practice Guidelines in Oncology. Drugs approved by the FDA for maintenance treatment of such patients are pemetrexed and erlotinib, and the NCCN also recommends bevacizumab and gemcitabine in appropriate patients. Docetaxel is also sometimes used in NSCLC MT, according to Marie-Anne Smit, MD, MS, and John L. Marshall, MD, in their recent review of MT in various types of solid tumors.2

Despite established standards, debate about the value and role of MT in NSCLC continues. Some argue that more evidence of the efficacy of MT is needed, adding that the tactic is costly and can increase toxicities for patients.

Dr. Corey Langer

Corey Langer, MD

But Corey Langer, MD, director of Thoracic Oncology at the Abramson Cancer Center and professor of Medicine at the University of Pennsylvania, is among those who tend to favor the strategy because its immediacy prevents treatment attrition following first-line therapy.

In Langer’s opinion, the toxicity associated with maintenance pemetrexed is minimal, and he’s seen it work well in patients.

“My record is a woman who’s on her 50th cycle with pemetrexed maintenance given every three weeks. That’s three years altogether— uncharted territory,” he said. “I hardly ever remember advanced lung cancer patients making it to a year or two, so having a debate at three or four years about whether to continue treatment is a nice dilemma.”

MT Is Standard in NSCLC

To Mark Kris, MD, chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center, there’s no question that MT has value in NSCLC.

“To me, it’s almost a no brainer that continuing a therapy that has proven to be effective and safe in a specific patient makes all the sense in the world—it’s the ultimate targeted therapy,” Kris said. “It gives such patients a longer time cancer-free and an improvement in survival measured in months. For those people in whom it’s safely given, effective, and not lifestyle-impeding, all the data from virtually every trial in NSCLC says it should be continued.”

Dr Mark G. Kris

Mark G. Kris, MD

“The PARAMOUNT trial3 that looked at maintenance therapy with pemetrexed—regardless of whether you measure the time from the start of treatment or the beginning of maintenance— demonstrated months of improved survival,” Kris said. “In POINTBREAK,4 although overall survival (OS) was the same, when you look specifically at patients who got maintenance therapy, giving them both pemetrexed and bevacizumab, rather than bevacizumab alone, resulted in longer survival, as well.”

In a debate during the 13th International Lung Cancer Congress in July 2012, Wakelee echoed Kris’s argument that MT is a valuable tool for managing NSCLC.

Wakelee described switch maintenance as a standard in the disease, noting that a progression-free survival (PFS) benefit has been demonstrated in all studies of that approach in NSCLC. In addition, she said, OS improved significantly with pemetrexed switch maintenance in the JMEN trial5 and with erlotinib switch maintenance in the SATURN trial,6 and strongly trended in favor of docetaxel as MT rather than second-line therapy in Fidias et al’s phase III study.7

Selected Phase III Maintenance Therapy Trials in Non–Small Cell Lung Cancer

Trial Design Results
CONTINUATION MAINTENANCE
PARAMOUNT3 pemetrexed maintenance vs placebo, following four cycles of pemetrexed plus cisplatin Median OS, 13.9 vs 11.0 months from randomization, 16.9 vs 14.0 months from induction, with pemetrexed vs placebo (HR = 0.78; P = .02)
Median PFS, 4.1 vs 2.8 months from randomization, with pemetrexed vs placebo (HR = 0.62; P <.0001)
POINTBREAK4 pemetrexed/carboplatin/bevacizumab, followed by pemetrexed/bevacizumab maintenance
vs
paclitaxel/carboplatin/bevacizumab, followed by bevacizumab maintenance
Overall: Median OS, 12.6 vs 13.4 months in pemetrexed vs paclitaxel arm (HR = 1.00; P = .949)
Median PFS, 6.0 vs 5.6 months in pemetrexed vs paclitaxel arm (HR = 0.83; P = .012)
Subgroup treated with maintenance:
Median OS, 17.7 vs 15.7 months in pemetrexed/bevacizumab vs bevacizumab arm
SWITCH MAINTENANCE
JMEN5 pemetrexed maintenance vs placebo, following four cycles of platinum-based chemotherapy OS, 13.4 vs 10.6 months, with pemetrexed vs placebo (HR = 0.79; P = .012)
PFS, 4.3 vs 2.6 months with pemetrexed vs placebo (HR = 0.50; P <.0001)
SATURN6 erlotinib maintenance vs placebo, following four cycles of platinum-based chemotherapy Overall: Median OS, 12.0 vs 11.0 months with erlotinib vs placebo (HR = 0.81; P = .0088)
Median PFS, 12.3 vs 11.1 weeks with erlotinib vs placebo (HR = 0.71; P <.0001)
EGFR-posltive patients:
Median PFS with erlotinib vs placebo: HR = .10; P <.0001
Fidias et al7 maintenance vs second-line docetaxel, following four cycles of gemcitabine/carboplatin Median OS, 12.3 vs 9.7 months, with maintenance vs second-line docetaxel (P = .0853)
Median PFS, 5.7 vs 2.7 months, with maintenance vs second-line docetaxel (P = .0001)



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