Theoretically you a correct Andreas that this was a superiority trial and that ni superiority in PFS was shown. On the other hand the clinical interpretation of the MITO7/ENGOT-ov10 study showed cleary that weekly paclitaxel at 60 mg/m² and carbo weekly AUC2 was at least as good in terms of PFS (18.3 versus 17.3 months  for weekly and 3-weekly respectively, HR: 0.96) and in QOL than the classical 3-weekly paclitaxel carbo regimen. The primary endpoint was originally only QOL and it was shown that FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]).

Do we really need to continue advocating e.g. complete alopecia in all our patients with paclitaxel-carboplatin 3-weekly as the only possible standard arm (something that can be avoided in most patients with the MITO7 weekly regimen with cold-cap), knowing that the efficacy and QOL of the weekly regimen is not inferior to three-weekly???

Thanks Andreas. I think indeed it is important to have the option of using the MITO regimen because QOL with this regimen was better (that was the first primary endpoint of MITO7 and planned in 350 patients) and because 4 trials (MITO7, ICON8, GOG262 and the Turbo study of Maria van der Burg) all showed a – non-significant – but somewhat higher PFS in the weekly arms. Anyhow no signal that PFS is worse with weekly.

Indeed with paclitaxel weekly 80 mg/m² the QOL data are worse (e.g. ICON8) but this is the opposite with the MITO7 regimen using 60 mg/m² paclitaxel in combination carbo AUC2 weekly.  Based on this evidence, many BGOG centres (and I suppose also MITO centers and others?) have shifted to the MITO7 regimen in first line (and it is an option for the standard arm in the ENGOT-ov43).

Also, hair loss Grade 2 was significantly lower in MITO7 study (weekly 29%, 3-weekly 59%) In addition, in our experience when using the MITO7 regimen in combination with cold caps, 96% of our patients do not need  a wig.  Something the majority of our patients value very high.

Finally I believe that for Japanese (Asian?) patients the JGOG regimen should still be an option.

• This reply was modified 4 years, 10 months ago by Ignace Vergote.

I completly  support the point to exclude LGSC of the discussion for NACT looking to the data reported on low sensitivity to platinum based CT

and this will help us to developp new trial involving new drug in this landscape

I support Andreas point. No evidence the weekly regimen is equal to three weekly in the MITO trial. Qol data very difficult to interpret !!

but the trials are developped as superioty trial not equivalent, a meta analysis should be proposed

There is a Cochrane meta-analysis of first line weekly trials ongoing at the moment which may give further evidence.

No data of weekly paclitaxel in recurrent setting after weekly paclitaxel upfront

For future trials QoL should be a co-primary end point (as in MITO trial)

but the trials are developped as superiority trial not equivalent, a meta analysis should be proposed

I would agree with a meta analysis, but for now I think Andreas’ comments are the most scientifically valid and that 3 weekly carboplatin/taxol should remain the “reference” arm  for  studies where the aim is to assess superiority of an alternative regimen.  However, it need not always be the “control” arm.  If we consider that the MITO7 regimen is likely to remain in clinical practise then it seems a reasonable option for it to be a control arm, particularly for studies where the primary focus is QOL or in studies involving older/frailer patients.  I think the latter studies are an important unmet need.

I support Ignace.

I believe that one of the important roles of phase III randomized controlled trials is to determine whether the results can be extrapolated to daily clinical practice. From this point of view, it would be better to add treatments that are currently widely used in daily clinical practice as standard treatment options, even if they have some scientific issues.

In clinical practice, weekly schedules are a valid option, with 4 trials showing (not proving) equal effectivity. Looking forward to  the Cochrane meta-analysis of first line weekly trials