Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
recommended for tumors expressing P790M (Jänne, 2015). In tumors bearing
ALK-/ROS-gene-rearrangements ceritinib is approved and recommended in
case of crizotinib resistance (Shaw, 2014). Conclusion: During the past ten
years the complexity of the treatment algorithm of advanced NSCLC has
gradually increased by the incorporation of several approved molecules. Novel
immunotherapies have recently changed the management of advanced wildtype
NSCLC. Treatment by histo-type and geno-type has been established and
it can be assumed by the given speed of growth of molecular information that
the process of treatment differentiation will fast continue. Identification
of new prognostic and predictive factors undoubtedly will accelerate this
process.
SESSION MTE17: MAINTENANCE THERAPY VERSUS EARLY
SECOND-LINE THERAPY IN ADVANCED NSCLC
(TICKETED SESSION)
TUESDAY, DECEMBER 6, 2016 - 07:30-08:30
MTE17.02 MAINTENANCE THERAPY VERSUS EARLY SECOND-LINE
THERAPY IN ADVANCED NSCLC
Panos Fidias
Massachussets General Hospital, Boston/United States of America
Several trials have evaluated the appropriate initial duration of platinum
based chemotherapy: 3 versus 6 cycles, 4 versus continuous cycles, or 2 versus
4 cycles after non-progression to the initial 2 treatments. In all situations
there was no benefit to longer duration of chemotherapy and both ASCO and
NCCN recommend no more than 6 cycles of initial treatment. Continuation of
lower intensity therapy (typically with a single agent from the initial doublet)
was also tested. Studies of weekly paclitaxel after carboplatin-paclitaxel
(Belani et al) or gemcitabine after cisplatin-gemcitabine (Brodowicz et al)
showed no OS difference, but a possible benefit in PFS. Studies evaluated the
introduction of a non-cross resistant agent (early second line) in patients
without progression after initial chemotherapy. Westeel et al. randomized
patients after MIC x 3 to either observation versus vinorelbine; Fidias et al.
evaluated immediate versus delayed docetaxel after carboplatin-gemcitabine
x 4 and JMEN study looked into pemetrexed versus placebo after four cycles of
platinum doublet. For the latter two studies, about 50% of patients
completed 6 maintenance cycles and 50-60% of patients in the observation
arm received second line therapy; this is consistent with rates of second line
therapy in multiple studies of NSCLC. Results showed a 2-3 month difference
in PFS favoring immediate therapy. In terms of overall survival, there was no
difference with vinorelbine, and a 2.6-2.8 month difference with either
docetaxel or pemetrexed (significant only with pemetrexed). QoL was not
affected by continuous chemotherapy and tumor related symptoms improved
with pemetrexed. Erlotinib has been evaluated in 3 randomized trials against
placebo (SATURN), observation (IFCT-GFPC 0502) or in combination with
bevacizumab against placebo-bevacizumab (ATLAS). In all studies there was a
PFS benefit (HR 0.71-0.82), but OS was only significant in the SATURN trial (HR
0.81). PFS benefit was limited to non-squamous histology for pemetrexed, as
opposed to the docetaxel and erlotinib trials. Despite the initial negative
trials, continuation pemetrexed following platinum-pemetrexed doublet has
emerged as a standard option for non-squamous NSCLC. PARAMOUNT
randomized between pemetrexed and placebo following four cycles of
cisplatin pemetrexed. It showed a PFS benefit (HR 0.64) and also an OS
benefit (2.9 month difference, HR 0.78) in favor of continuation maintenance.
AVAPERL used a similar design, however with the addition of bevacizumab
throughout therapy, i.e. initial cisplatin-pemetrexed-bevacizumab followed
by pemetrexed-bevacizumab versus bevacizumab. PFS significantly favored
pemetrexed (10.2 versus 6.6 months), and although OS was also superior (19.8
versus 15.9 months) it was not statistically significant. The IFCT-GFPC 0502
trial also evaluated continuation gemcitabine and demonstrated a PFS
advantage, but no OS benefit in an underpowered study. Bevacizumab
continuation is an accepted approach based on the design of E4599, although
its contribution has never been established in a randomized trial. However, a
direct comparison between E4599 (carboplatin-paclitaxel-bevacizumab
followed by bevacizumab) and carboplatin-pemetrexed-bevacizumab
followed by pemetrexed-bevacizumab was undertaken in the POINTBREAK
study. It showed no OS differences (numerically favored E4599: 13.4 versus
12.6 months), although in pre-specified analysis of patients going through
maintenance (as opposed to ITT) there was a 2-month difference favoring the
combination of pemetrexed-bevacizumab. E5508 [ClinicalTrials.gov
identifier:NCT01107626] is attempting to answer this question by directly
randomizing patients to either bevacizumab, pemetrexed or the combination
after carboplatin-paclitaxel-bevacizumab. Subset data from the SATURN trial
strongly supports switch maintenance with erlotinib for EGFR mutant
patients, who had an impressive three fold higher median PFS (44 vs 14 weeks;
HR: 0.10; 95% CI: 0.04–0.25). INFORM included 296 asian patients, who were
randomized between gefitinib and placebo. PFS favoured gefitinib
maintenance (4.8 vs 2.6 months, HR=0.42; 95% CI: 0.33–0.55; p