Maintenance Chemotherapy in Ovarian Cancer: A Trial-Sequential Analysis 1243
Figure 1. Maintenance chemotherapy versus observation in
ovarian cancer: trial sequential analysis of 4 randomized
trials (end-point = progression). The z-curve (in blue) is
composed of consecutive segments that correspond to indi-
vidual trials; trials are plotted in chronological order (from
left to right). The x-axis indicates the cumulative number of
patients. At the cumulative number of 541 included patients,
the curve has crossed the boundaries of futility. The optimal
information size is 836 patients. Abbreviations and sym-
bols: red lines are the boundaries for superiority or inferi-
ority; green lines are the boundaries for futility. T, treat-
ment group; C, control group.
size was estimated at a cumulative number of 836 pa-
tients, the 4 trials involving a total of 514 patients were
already sufficient to prove futility.
The conclusion of our analysis depends on whether or
not the threshold of incremental effectiveness (i.e. RRR
= 20%) is agreed upon or, in other words, if this thresh-
old is assumed to reasonably reflect the criterion of cli-
nical relevance. One should keep in mind that, in disease
conditions in which life expectancy is relatively short, a
RRR of 20% generally translates into an absolute sur-
vival improvement of only a few months; hence, if one
considers that median PFS in these patients is slightly
more than 24 months [6], a relative improvement of 20%
corresponds to an absolute improvement in median PFS
of less than 5 months, which can be considered an ac-
ceptable threshold in terms of clinical relevance.
3. Conclusion
In conclusion, if our assumptions are accepted, the re-
sults of our analysis can be seen as the proof of no effec-
tiveness of maintenance chemotherapy in ovarian cancer
based on conventional cytotoxic agents. Consequently,
no further trials of this type should be performed to as-
sess the effectiveness of this intervention in this clinical
condition.
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