Winfree KB, Ainsworth C, Njue A, Molife C, Lyall M, Jen MH, Bittoni M, Heyes A, Carbone DP. Novel antiangiogenic drugs, immune checkpoint inhibitors, and chemotherapy in patients with aNSCLC who have aggressive disease: a systematic review. J Clin Oncol. 2018 May 16;36(15_suppl):e21120-e. doi: 10.1200/JCO.2018.36.15_suppl.e21120

BACKGROUND: This review aimed to summarize the clinical utility (efficacy, safety, and quality of life) of ramucirumab compared to nintedanib, immune checkpoint inhibitors (ICIs), and chemotherapy in second-line treatment for patients with advanced non-small cell lung cancer (aNSCLC) who do not respond well to first-line treatment (1LT) due to aggressive tumor behavior.

METHODS: We systematically searched the literature (database inception through October 2017) to identify randomized, controlled trials reporting efficacy and/or safety of ramucirumab, nintedanib, ICIs (atezolizumab, avelumab, durvalumab, nivolumab, or pembrolizumab), or chemotherapy (docetaxel, gemcitabine, nab-paclitaxel, paclitaxel, pemetrexed, or vinorelbine) in aNSCLC patients with aggressive disease (AD) characteristics, as defined by physician opinion.

RESULTS: The 14 identified studies had ≥ 1 subgroups with characteristics associated with AD: refractory and/or progressive disease (PD) as best response to prior treatment (11 studies), rapid progression (2), short duration on previous treatment (1), high tumor burden or size (2), and short duration since start of last treatment (4). Survival estimates were reported in 11 studies; response and safety data were available for 2 studies. Ramucirumab plus docetaxel and nintedanib plus docetaxel showed efficacy in patients with < 9 months since start of 1LT or with PD as best response to 1LT. For these two subgroups, both treatments had safety outcomes consistent with the overall aNSCLC population. Docetaxel and pemetrexed were beneficial in patients with < 3 months since start of 1LT and with PD as best response to 1LT, respectively. No studies reported on ICIs for AD. Varying definitions of AD and the lack of a common comparator limited indirect treatment comparisons of trials.

CONCLUSIONS: There is limited evidence for patients with AD. Recent subgroup data for ramucirumab and nintedanib demonstrate benefit in patients with varying AD definitions. AD in the 1LT setting may be a poor prognostic factor for survival based on identified studies. Further studies assessing treatment benefits in aNSCLC patients with AD are needed.

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