Table 1 Definition of PFS and progression

1.)

PFS will be determined as the time from the date of registration until the date that progression is determined or the date of death for any reason, whichever is sooner.

2.)

“Progression (PD)” means both PD confirmed by routine diagnostic imaging in each course and PD confirmed by as-needed diagnostic imaging in the case that there is clinical suspicion of PD. In the latter case, it is preferable that there is at least objective evidence.

3.)

When progression is determined based on diagnostic imaging, the date of progression will be the date on which imaging is assessed. When clinical progression is first determined independently of diagnostic imaging, and then later objectively determined on the basis of diagnostic imaging, the date of progression will be back-dated to the date of determination of clinical progression. If no objective evidence is obtained, it will be treated as a censoring event in the formal analysis, and sensitivity analysis will be also conducted as if this were PD.

4.).

When considering tumor regrowth and determining PD according to RECIST, it is considered a PD as PFS event regardless of tumor diameter. But even if it is decided as PD according to RECIST, investigators can continue the protocol treatment if they consider continued treatment to be beneficial to the patient.

5.)

If treatment discontinuation is needed due to symptomatic deterioration without any objective evidence at that time, it is reported as “symptomatic deterioration”. Investigators should endeavor to obtain objective evidence of the progression even after discontinuation of treatment. In this case, the event shall be judged to be clinical PD and handled as mentioned in 2) above. When progression is determined on the basis of diagnostic imaging, the date of progression will be back-dated to the date of diagnosis of symptomatic deterioration.

6.)

Survivors for whom progression has not been determined will be censored based on the last date on which the absence of progression was clinically confirmed (the last day that PFS was confirmed).

7.)

Cases of discontinuation of protocol treatment because of toxicity or patient refusal, even if another therapy is added as a post-treatment, will be censored at the date of discontinuation or the date that post-treatment was started.

8.)

In cases where progression is diagnosed on the basis of imaging, the event will be determined based not on evaluation dates where the result is “suspected” on imaging but on a subsequent evaluation date where progression is “confirmed” on imaging.

9.)

Secondary cancer (multiple cancers in metachronous) will not be regarded as either an event or censored.