Two of the meta-analyses reported a statistically significant improvement in OS with switch maintenance but not with continuous, and one demonstrated no difference in OS, Goss reported.
Goss argued that “no trial has demonstrated an improvement in quality of life with MT versus observation—not one,” although some showed no deterioration in quality of life. In addition, he said, three of the meta-analyses showed an increased adverse event (AE) rate in the maintenance arm; the fourth didn’t evaluate AEs.
Finally, Goss said, in the majority of cases, it’s not clear which patients are likely to benefit from MT.
“We desperately need good biomarkers of efficacy if we’re going to persist with this strategy,” he said.
According to Gerber and Schiller, though, there are already some predictors that can help identify which patients will benefit from MT.
Depending on the type of drug patients with NSCLC are scheduled to receive, the authors wrote, those factors can include stable disease after chemotherapy; good performance status; potential obstacles to receiving second-line therapy at disease progression; adenocarcinoma, rather than squamous cell, histology; and EGFR mutations.
Langer added that there might be stronger evidence to support the value of MT in lung cancer if trials had been designed differently.
“I think the reason there’s so much criticism, and that you haven’t seen wholesale adoption of maintenance therapy, is the lack of mandatory crossover of the control arm to the maintenance therapy drug at progression,” which would have protected against inadvertent bias, Langer said. “That was done in the Fidias trial [immediate versus delayed docetaxel],” Langer said, “and if it had been done in the Ciuleanu paper [maintenance pemetrexed versus placebo] and we had still seen a survival advantage, the use of maintenance therapy would have gone up.”
MT Established in Some Breast Cancers
The use of MT in breast cancer is based on studies, over the last 10 years, that have shown it delays disease progression, Tripathy said. However, he cautioned, the studies have found little evidence that MT increases OS for patients with breast cancer.
According to Smit and Marshall in their review of MT in solid tumors, the strategy is standard in two types of breast cancer.
Anti-estrogen or aromatase inhibitor continuation therapy is the go-to strategy for patients with estrogen receptor (ER)– and/or progresterone receptor (PR)–positive metastatic breast cancer (MBC), they wrote. The technique, they specified, is often used after the cancer has been treated with surgery and chemotherapy and no evidence of disease remains.
According to Tripathy, such adjuvant therapy is not typically considered to be MT. But a similar tactic, in cases where ER- or PR-positive breast cancer is growing rapidly or has affected organs, does fall into the MT category, he said. Patients with that kind of disease, he said, might start with chemotherapy and then be given switch maintenance with up to 5 years of a hormonal therapy, such as tamoxifen, for premenopausal women or an aromatase inhibitor for postmenopausal women.
Meanwhile, in advanced HER2-positive breast cancer, the typical treatment is 3 or 4 months of chemotherapy with trastuzumab, and then, if the tumor is shrinking and the patient is experiencing side effects, maintenance with trastuzumab alone until disease progression or side effects that interfere with quality of life, Tripathy said.
Finally, if a tumor in advanced breast cancer is both ER-negative and HER2-negative, the only available treatment is chemotherapy, which can continue as long as the benefits outweigh the side effects, Tripathy said. “Sometimes, if a patient is on two chemotherapies, we might drop one and continue the other, and some people call that maintenance therapy,” he said. “It’s a matter of semantics.”
In breast cancer, MT with chemotherapy is much less common than maintenance with other types of agents, added Tripathy, who described the practice as “controversial.”
“There have been some studies with MT chemotherapy in breast cancer,” he said, “but it’s not like in lung cancer, where we have a series of trials that have shown that it clearly improves outcomes and the FDA has approved chemo in the MT setting.”
Maintenance with chemotherapy is being studied in patients with HR-negative or rapidly progressing MBC, or with visceral or endocrine therapy– resistant disease, Smit and Marshall pointed out. Several agents have been evaluated, the colleagues wrote, including pegylated liposomal doxorubicin (PLD), IL-2 with 13-cis retinoic acid, paclitaxel, and capecitabine, with only PLD demonstrating an improvement in time to progression (TTP) in the phase III GEICAM 2001-01 trial.13
That trial compared PLD with observation in patients who had initially been treated with doxorubicin and docetaxel. In the PLD arm, TTP was significantly improved by 3.3 months (8.4 vs 5.1 months; hazard ratio = 0.54; P
= .0002), but a modest increase in survival was not significant.