Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST)

C Boni, M Tiseo, L Boni, E Baldini, F Recchia, C Barone, F Grossi, D Germano, E Matano, G Marini, R Labianca, F Di Costanzo, A Bagnulo, C Pennucci, C Caroti, M Mencoboni, F Zanelli, T Prochilo, M A Cafferata, A Ardizzoni, Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), C Boni, M Tiseo, L Boni, E Baldini, F Recchia, C Barone, F Grossi, D Germano, E Matano, G Marini, R Labianca, F Di Costanzo, A Bagnulo, C Pennucci, C Caroti, M Mencoboni, F Zanelli, T Prochilo, M A Cafferata, A Ardizzoni, Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)

Abstract

Background: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G).

Methods: A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets.

Results: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens.

Conclusions: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

Figures

Figure 1
Figure 1
CONSORT diagram of the study. A total of 417 patients (96.3%) received study treatment consisting of at least one dose of chemotherapy. *One patient was assigned to the GP arm but received GN treatment. This patient was included in the GN arm for the safety analysis. GP, gemcitabine–cisplatin; GN, gemcitabine–vinorelbine; GIP, gemcitabine–ifosfamide–cisplatin; GIN gemcitabine–ifosfamide–vinorelbine.
Figure 2
Figure 2
Kaplan–Meier overall survival (OS) and progression-free survival (PFS) curves for two comparisons. (A, C) N-containing versus P-containing regimens; (B, D) 3- versus 2-drug regimens. N, vinorelbine; P, cisplatin.

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