. 2024 Nov 25;33(12):e70049. doi: 10.1002/pds.70049

TABLE 1.

Proposed rules for LOT determination from real‐world treatment regimens.

Rule	Line of therapy stays the same	Example regimen change	Example LOT determination	Number of times rule is applied in the ATOMIC EGFR cohort
1	If any agent is introduced within 28 days of the start of the first regimen of the current LOT	Day 0–21: Carboplatin, Pemetrexed Day 14–400: Brigatinib	0.5L ^a (Day 0–21): Carboplatin + Pemetrexed 1 L (Day 14–400): Brigatinib	109
2	If an angiogenesis inhibitor (e.g., bevacizumab, ramucirumab) is introduced within 90 days from the start of the first regimen of the current LOT	Day 0–80: Osimertinib Day 80–200: Osimertinib, Bevacizumab	1 L (Day 0–200): Osimertinib + Bevacizumab	1
3	If the gap between the end of the prior and the start of the current regimens is ≤ 60 days and the current regimen uses the same agent(s), an exchange of interchangeable agents (e.g., Carboplatin/Cisplatin, Paclitaxel/Nab‐paclitaxel), or a reduced regimen	Day 0–30: Entrectinib Day 80–110: Entrectinib	1 L (Day 0–110): Entrectinib	224

Rule

Line of therapy stays the same

Example regimen change

Example LOT determination

Number of times rule is applied in the ATOMIC EGFR cohort

If any agent is introduced within 28 days of the start of the first regimen of the current LOT

Day 0–21: Carboplatin, Pemetrexed

Day 14–400:

Brigatinib

0.5L ^a (Day 0–21):

Carboplatin + Pemetrexed

1 L (Day 14–400):

Brigatinib

109

If an angiogenesis inhibitor (e.g., bevacizumab, ramucirumab) is introduced within 90 days from the start of the first regimen of the current LOT

Day 0–80:

Osimertinib

Day 80–200:

Osimertinib,

Bevacizumab

1 L (Day 0–200):

Osimertinib + Bevacizumab

If the gap between the end of the prior and the start of the current regimens is ≤ 60 days and the current regimen uses

the same agent(s),
an exchange of interchangeable agents (e.g., Carboplatin/Cisplatin, Paclitaxel/Nab‐paclitaxel), or
a reduced regimen

Day 0–30:

Entrectinib

Day 80–110:

Entrectinib

1 L (Day 0–110):

Entrectinib

224

Rule	Line of therapy advances	Example regimen change	Example LOT determination
4	If an angiogenesis inhibitor (e.g., bevacizumab, ramucirumab) is introduced > 90 days after the start of the first regimen of the current LOT.	Day 1–120: Osimertinib Day 121–160: Osimertinib + ramucirumab	1 L (Day 1–120): Osimertinib 2 L (Day 121–160) Osimertinib + ramucirumab	22
5	If the gap between the end of the prior and the start of the current regimens is > 60 days and the current regimen uses the same agent(s), an exchange of interchangeable agents (e.g., Carboplatin/Cisplatin, Paclitaxel/Nab‐paclitaxel), a reduced regimen	Day 1–200: Alectinib Day 300–400: Alectinib	1 L (Day 1–200): Alectinib 2 L (Day 300–400): Alectinib	34
6	If a new non‐interchangeable agent is added to a regimen or is introduced after the discontinuation of all prior agents > 28 days after the start of the first regimen of the current LOT.	Day 1–42: Carboplatin + pemetrexed Day 43–700: Lorlatinib	1 L (Day 1–42): Carboplatin + pemetrexed 2 L (Day 43–700) Lorlatinib	1645

Rule

Line of therapy advances

Example regimen change

Example LOT determination

If an angiogenesis inhibitor (e.g., bevacizumab, ramucirumab) is introduced > 90 days after the start of the first regimen of the current LOT.

Day 1–120: Osimertinib

Day 121–160: Osimertinib + ramucirumab

1 L (Day 1–120): Osimertinib

2 L (Day 121–160)

Osimertinib + ramucirumab

If the gap between the end of the prior and the start of the current regimens is > 60 days and the current regimen uses

the same agent(s),
an exchange of interchangeable agents (e.g., Carboplatin/Cisplatin, Paclitaxel/Nab‐paclitaxel),
a reduced regimen

Day 1–200: Alectinib

Day 300–400: Alectinib

1 L (Day 1–200): Alectinib

2 L (Day 300–400): Alectinib

If a new non‐interchangeable agent is added to a regimen or is introduced after the discontinuation of all prior agents > 28 days after the start of the first regimen of the current LOT.

Day 1–42: Carboplatin + pemetrexed

Day 43–700: Lorlatinib

1 L (Day 1–42): Carboplatin + pemetrexed

2 L (Day 43–700)

Lorlatinib

1645

Abbreviation: LOT, line of therapy.

^{^a}

When a regimen is discontinued followed by the start of a new regimen all within 28 days of the start of the first line of therapy, the first regimen is assigned a line number of 0.5 while still being considered part of first‐line therapy.