Efficacy Of Pemetrexed As Second-Line Therapy In Advanced Nsclc After Either Treatment-Free Interval Or Maintenance Therapy With Gemcitabine Or Erlotinib In Ifct-Gfpc 05-02 Phase Iii Study.

7574 Background: Continuous exposure of tumor cells to maintenance therapy in advanced NSCLC might lead to resistance to subsequent treatments. IFCT–GFPC 0502 study showed a progression-free survival (PFS) benefit with gemcitabine (G) or erlotinib (E) maintenance compared to observation (O) after cisplatin-G induction chemotherapy. The trial included a pre-defined second-line therapy with pemetrexed (P), allowing post-hoc assessment of its efficacy according to previous maintenance treatment or treatment-free interval. Methods: Stage IIIB/IV NSCLC patients (pts) with a PS of 0-1 were randomized after 4 cycles of cisplatin-G chemotherapy to O or to receive maintenance therapy with G or E until disease progression. P was given as second-line treatment on disease progression in all arms. PFS and OS were assessed from the beginning of P therapy according to randomization arm. Tumor response to P and tolerance were also analyzed. Results: Of the 464 pts randomized to either O (155), G (154) or E (155), 360 pts (78 %) received P as second-line therapy, i.e. 130 (84%), 114 (74%) and 116 (75%) in O, G and E arm, respectively. Baseline characteristics remained well balanced between arms (overall median age of 58 years, 28% female, 91% stage IV, 41% PS 0, 65/19/16%, adenocarcinoma/squamous/other, 10% non-smokers and 56% responders to induction CT). Median number of delivered P cycles was 3 (1-40) in all arms. Response rate was 19%, 7% and 15% for non-squamous pts in O, G and E, respectively. Median PFS did not significantly differ between G and O (4.2 vs 3.9 months, HR [95% CI] 0.81 [0.62-1.06]) or E and O (4.2 vs 3.9 months, HR 0.83 [0.64-1.09]). OS data showed a non-significant improvement with G vs O (HR 0.81 [0.61-1.07]) or E vs O (HR 0.80 [0.61-1.05]), with a median of 7.5, 8.3 and 9.1 months for O, G and E, respectively. Results were similar when analysis was restricted to non-squamous pts. Grade 3-4 treatment-related AEs were similar in O (33.1%), G (31.6%) and E (25%). Conclusions: Maintenance therapy with continuation of G or switch to E does not impair the efficacy of second-line P by comparison with administration after a treatment-free interval.