Lume-lung 2: A multicenter, randomized, double-blind, phase III study of nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy.

• DOI: 10.1200/jco.2013.31.15_suppl.8034
• Publication Date: 2020-03-11T15:43:13Z
• Authors: Nasser H. Hanna; Rolf Kaiser; Richard N. Sullivan; Osvaldo Rudy Aren; Myung-Ju Ahn; Beatrice Tiangco; Zanete Zvirbule; Carlos H. Barrios; Ahmet Demirkazik; Birgit Gaschler-M...; Isabelle Voccia; Jose Barrueco; Joo-Hang Kim
• Keywords: Pemetrexed; Clinical endpoint; Intention-to-treat analysis

8034 Background: Nintedanib (N) is an oral inhibitor of VEGFR, FGFR, and PDGFR. This global phase 3 study investigated the safety efficacy N + pemetrexed (PEM) vs placebo (P) PEM in patients (pts) with advanced, non-squamous NSCLC previously treated chemotherapy. Methods: Pts were randomized 1:1 to 200 mg po bid 500 mg/m 2 iv q21d (n=353, Arm A) or P (n=360, B). Continuation until PD unacceptable toxicity N, P, PEM, a combination was permitted. 1° endpoint centrally reviewed PFS. The null hypothesis tested on ITT population after 394 events had occurred (two sided α=5%). 2° endpoints included OS, investigator-assessed PFS, response rate (RR), safety, QoL. Results: Baseline pt characteristics balanced between A B (median age 59 y, female 45–42%, ECOG PS 1 62-61%, adenocarcinoma 95–93%, prior bevacizumab 8%). Based planned DMC futility analysis enrolment halted randomizing 713/1300 pts (no issues identified). Ongoing unblinded follow-up continued per protocol. Subsequent (centrally PFS) favored 4.4 3.6 mo, HR 0.83 [95% CI: 0.7–0.99], p=0.04). Disease control also significantly improved N-treated (61 53%, odds ratio 1.37, p=0.039). No difference OS (HR 1.03) RR (9%) found. Exploratory analyses identified time since start st -line therapy as predictive marker outcome (ASCO 2013). There no increase SAEs G5 AEs PEM. Addition resulted higher incidence ≥G3 elevated ALT (23 7%), AST (12 2%), diarrhea (3 1%), but hypertension, bleeding, thrombosis, mucositis, neuropathy. Conclusions: met even though stopped prematurely. Treatment PFS advanced chemotherapy, manageable profile. Clinical trial information: NCT00806819.