Is time to progression associated with post-progression survival in previously treated metastatic non-small cell lung cancer with BRAF V600E mutation? A secondary analysis of phase II clinical trial data

Junlong Li, Medha Sasane, Jie Zhang, Jing Zhao, Marie Louise Ricculli, Zhiwen Yao, Suman Redhu, James Signorovitch, Junlong Li, Medha Sasane, Jie Zhang, Jing Zhao, Marie Louise Ricculli, Zhiwen Yao, Suman Redhu, James Signorovitch

Abstract

Objective: Longer time to progression (TTP) is associated with prolonged post-progression survival (PPS) in anaplastic lymphoma kinase+non-small cell lung cancer (NSCLC). This study evaluated whether TTP is associated with PPS among previously treated patients with metastatic v-Raf murine sarcoma viral oncogene homolog B V600E NSCLC receiving dabrafenib as monotherapy or in combination with trametinib.

Design: Secondary analysis of phase II clinical trial data.

Setting: Patients who experienced disease progression treated with dabrafenib monotherapy or in combination with trametinib as second line or later in an open-label, non-randomised, phase II study.

Primary outcome measures: The primary outcome was the TTP-PPS association. PPS was assessed with Kaplan-Meier analysis among patients with shorter versus longer TTP (< or ≥6 months). The TTP-PPS association was quantified in the Cox models adjusting for clinical covariates.

Results: Of the 84 included patients who progressed on dabrafenib monotherapy (n=57) or combination therapy (n=27), 60 (71%) died during post-progression follow-up. Patients with TTP ≥6 months experienced significantly longer PPS compared with those with TTP <6 months (median PPS: 9.5 vs 2.7 months, log-rank p<0.001). Each 3 months of longer TTP was associated with a 32% lower hazard of death following progression (HR 0.68, 95% CI 0.52 to 0.88) in the multivariable Cox model. Similar associations were seen in each treatment arm.

Conclusion: A longer TTP duration after treatment with dabrafenib monotherapy or combination therapy was associated with significantly longer PPS duration.

Trial registration number: NCT01336634; Post-results.

Keywords: BRAF V600E NSCLC; dabrafenib; oncology; post-progression survival; time to progression; trametinib.

Conflict of interest statement

Competing interests: JieZ and SR are employees of Novartis Pharmaceuticals Corporation and own stock/stock options. MS was a previous employee of Novartis. JL, JingZ, MLR, ZY and JS are employees of Analysis Group, which has received consultancy fees from Novartis Pharmaceuticals Corporation.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Sample selection flow chart. Patient-level data were used from the non-randomised, open-label, phase II trial BRF113928 (data cut: 7 October 2015, trial ongoing).
Figure 2
Figure 2
Kaplan-Meier analysis of PPS in the combined cohort, stratified by duration of TTP. PPS, post-progression survival; TTP, time to progression.

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Source: PubMed

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