“In addition, as described in the 2018 FDA guidance document for...

“In addition, as described in the 2018 FDA guidance document for clinical trial endpoints, time-to-event measures such as overall survival aredifficult to interpret in single-arm trials, and Study 001 was not designed to detect differences in survival. And therefore, survival endpoints will not be discussed further by FDA.”

Yep Reg … now go to the 2018 guideline reference in the quote and page 7.
https://www.fda.gov/media/71195/download

“Overall survival should be evaluated in randomized controlled studies. Data derived from externally controlled trials are seldom reliable for time-to-event endpoints, including overall survival. Apparent differences in outcome between external controls and current treatment groups can arise from differences other than drug treatment, including patient selection, improved imaging techniques, or improved supportive care. Randomized studies minimize the effect of these known and unknown differences by providing a direct outcome comparison.”

“Seldom reliable”.

Now thinking cap on. If survival analyses from single arm trials are “seldom reliable” would those analyses be any more reliable with longer or shorter follow-up periods.

Answer – it would make very little difference. But on balance survival analyses from single arm trials would be expected to become less reliable with a longer follow-up because patients would be more likely to have other treatments. The time to event endpoint will become more confounded over time … not less.

The basic point from @whytee is 100% correct. The cornerstone to the resubmission is survival analysis from a single arm trial that the FDA views as difficult to interpret because they are “seldom reliable”.

It’s a weak as it gets. And that’s before you even drill down on the key comparison to the MacMillan paper study