Maintenance therapy in NSCLC is an ever-contentious issue,” stated formal discussant of these trials, Martin Edelman, MD, University of Maryland Greenebaum Cancer Center, Baltimore, at the ASCO Annual Meeting. “The maintenance approach is based on two observations: limited benefit from more than four courses of chemotherapy and improved outcomes with second-line chemotherapy.”

There are two approaches: continued maintenance (exemplified by the PARAMOUNT trial) and switch maintenance (the INFORM study). “These studies raise more questions than answers,” Dr. Edelman said.

He questioned the value of progression-free survival as an endpoint. “It is subject to bias and doesn’t answer the question about overall survival. Is maintenance therapy really beneficial? The quality-of-life data are disappointing, with no difference between treatment arms. Maintenance therapy is not cost-free,” he continued.

Concerns and Conjectures

His biggest concern is the fate of patients on the control arms of these trials.  Many of these patients never get second-line therapy, yet we know that second-line therapy works, so the control arm results will be inferior. This is not a trivial issue. In my opinion, second-line therapy should be introduced when the tumor regrows,” he told listeners.

It is not clear whether responders or nonresponders to induction therapy should go on to maintenance therapy. Also, almost all of the advantages with an EGFR tyrosine kinase inhibitor occur in patients with activating EGFR mutations. “I would like to see quality-of-life data on patients with activating EGFR mutations,” he said. EGFR mutations predict progression-free survival, not overall survival, he added.

 “We learned [from these trials] that the drugs work in patients who derive benefit from first-line chemotherapy. To date, there is no evidence that early introduction of therapy will improve survival compared to introducing second-line therapy at disease progression,” he said.

Dr. Edelman said that future trials should mandate second-line therapy at progression, documentation of nontreatment in the control arm, and outcomes reporting for patients who get treatment on the control arm. ■

Disclosure: Dr. Edelman has been a consultant for Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Endocyte, Genentech, Lilly, and OSI Pharmaceuticals, and has received research funding from Bristol-Myers Squibb, Lilly, and Tragara.