Table 2 Types of post-progression therapy, with examples and description

Substandard post-progression therapy

OR

Low cross-over rate

(to a therapy with proven efficacy in later lines)

LATITUDE trial [10]

- Abiraterone versus placebo in addition to ADT^a

in castrate sensitive metastatic prostate cancer

- Limited access to abiraterone at progression in the control arm,

with 24% of patients treated upon progression receiving abiraterone

With substandard access to optimal post-progression treatment in the control arm (either within the protocol, or outside the protocol), this may favor the experimental arm

NO

Standard post-progression therapy

OR

High cross-over rate

(to a therapy with proven efficacy in later lines)

PROFILE 1014 trial [11]

- Crizotinib versus chemotherapy

in first-line ALK-positive non-small cell lung cancer

- Upon progression in the control arm, 98% of treated patients received a TKI

YES

Crossover to a therapy with unproven efficacy in later lines

(either within or outside the protocol)

POLO-trial [12]

- Olaparib versus placebo as maintenance after first-line chemotherapy

in germline BRCA-mutated metastatic pancreatic cancer

- 15% of patients received a PARP inhibitor upon progression in the control arm

(with unproven efficacy at progression)

With crossover to a therapy with unproven efficacy,

this may alter the correct interpretation of overall survival results (e.g. incorrectly attributing lack of survival benefit to crossover)

NO

No crossover to a therapy with unproven efficacy in later lines

(either within or outside the protocol)

NGR015 trial [13]

- NGR-hTNF versus placebo (plus best investigator choice) in second-line pleural mesothelioma

- No patient received the investigational agent (NGR-hTNF) upon progression

YES

Low access to any post-progression therapy

MONALEESA-7 trial [14]

- Ribociclib versus placebo (plus endocrine therapy)

in mostly first-line hormone positive metastatic breast cancer

- 73% received any therapy at progression in the control arm, 69% in the experimental arm, far less than in the real life

With limited access to any post-progression treatment in both arms (including the control arm), this may favor the experimental arm by limiting the “dilution” of benefit that could have occur with optimal access to standard subsequent lines

NO

High access to any post-progression therapy

FRENCH-LUNG-CANCER-GROUP [15]

- Carboplatin plus etoposide versus topotecan

in second-line small cell lung cancer

- 63% of patients received a 3rd line

YES