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

BMJ Open. 2018 Aug 17;8(8):e021642


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.


Secondary analysis of phase II clinical trial data.


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.


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


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.


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

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Li J, Sasane M, Zhang J, Zhao J, Ricculli ML, Yao Z, Redhu S, Signorovitch J