Optimizing Maintenance Therapy in NSCLC

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Multiple clinical trials have explored maintenance strategies using a variety of therapies for patients with non-small cell lung cancer (NSCLC). Continuation maintenance using first-line treatments beyond progression are commonly utilized, whether they’re called maintenance therapy or not, notes Mark A. Socinski, MD. Switch maintenance approaches have been explored in a number of phase III studies, including the JMEN and SATURN trials.

In the SATURN study, erlotinib was compared with placebo following four cycles of first-line platinum-based chemotherapy. The median overall survival (OS) with erlotinib was 12.0 months versus 11.0 months with placebo (HR = 0.81; P = .0088). The median progression-free survival was 2.8 months with erlotinib versus 2.6 months with placebo (HR = 0.71; P <.0001).

In the JMEN study, pemetrexed was compared with placebo following four cycles of platinum-based chemotherapy. The median OS was 13.4 months versus 10.6 months (HR = 0.79; P = .012) and the median PFS was 4.3 months versus 2.6 months (HR = 0.50; P <.0001), for pemetrexed and placebo, respectively.

These studies were conducted without the use of bevacizumab, raising the question of whether this agent would add to the efficacy, notes Socinski. To address this, the phase III ATLAS trial added bevacizumab to erlotinib following first-line treatment with chemotherapy plus bevacizumab. This study showed a significant increase in PFS but not OS, Socinski notes.

Following the success of switch maintenance therapy with pemetrexed in the JMEN trial, the PARAMOUNT study explored the drug beyond progression on four cycles of pemetrexed plus cisplatin. In this study, the median OS was 13.9 months versus 11.0 months (HR = 0.78, P = .0195) and the median PFS was 4.1 months versus 2.8 months (HR = 0.62; P <.0001), for pemetrexed and placebo, respectively.

The next wave of trials sought to combine bevacizumab with pemetrexed in the POINTBREAK and AVAPERL studies, notes Socinski. In the POINTBREAK trial, patients received first-line pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed plus bevacizumab or first-line paclitaxel, carboplatin, plus bevacizumab followed by maintenance bevacizumab. Overall, this study failed to significantly extend OS.

In the AVAPERL study, patients received first-line bevacizumab, cisplatin, and pemetrexed for four cycles followed by maintenance bevacizumab alone or in combination with pemetrexed. The median PFS was 7.4 months with the combination versus 3.7 months for single-agent bevacizumab (HR = 0.48; P < .001), with OS data still pending.

A new study, ECOG5508, plans to build on evidence from previous studies, such as the JMEN trial, notes Heather A. Wakelee, MD. This study will compare maintenance therapy with bevacizumab and pemetrexed alone or in combination following four cycles of carboplatin, paclitaxel, and bevacizumab for patients with NSCLC. The study hopes to enroll 1282 patients. This study will provide a first head-to-head comparison of various maintenance strategies for NSCLC.