OBJECTIVES: In recent years, the treatment landscape in nsNSCLC has changed; new therapies (e.g. bevacizumab (BEV) indicated in 1L) have become available and other therapies (e.g. pemetrexed (PEM) in 1L and 2L) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is unclear how the therapy sequence rank in terms of best PFS for patients with nsNSCLC. METHODS: A therapy sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for PFS and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, receive first-line treatment with either BEV-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin (PEM+CIS)). Patients would then progress to a subsequent line therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy (based on EMA licensed therapies). Weibull distribution curves were fitted to the data. RESULTS: All BEV-based first-line therapy sequences analyzed achieved total PFS of more than 15 months. Bevacizumab-carboplatin-paclitaxel (1L) à pemetrexed (2L) à erlotinib (3L) à docetaxel (4L) resulted in total mean PFS time of 15.5 months, for instance. Sequences including PEM+CIS in first-line achieved total PFS times between 12.3 and 13.3 months with potentially (slightly) higher total PFS time achieved when assuming PEM continuation therapy in maintenance after PEM+CIS in 1L induction. CONCLUSIONS: The model suggests that treatment sequencing strategies starting with a BEV-based combination in 1L yield better PFS outcomes than those starting with PEM-based combinations due to the possibility of one further-line treatment starting with BEV-based combination.