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. 2023 Jan 5;29(7):1317–1331. doi: 10.1158/1078-0432.CCR-22-2274

Figure 2.

Figure 2. Lorlatinib treatment of Th-ALKF1174L/MYCN tumor-bearing animals gives a survival advantage over vehicle control. A, In vivo analysis of a panel of ALK inhibitors including crizotinib, ceritinib, alectinib, and lorlatinib was carried out using the Th-ALKF1174L/MYCN model. Tumor-bearing Th-ALKF1174L/MYCN mice, were treated with the indicated inhibitor or its corresponding vehicle (veh.) over a 3-day interventional dosing schedule, and tumor volume change was monitored by MRI on day 0 and day 3. Each bar represents tumor volume change in an individual animal. Crizotinib versus vehicle ****, P < 0.0001. Alectinib versus vehicle **, P = 0.0021. Lorlatinib versus vehicle. ***, P = 0.0002. B, Tumors from A were harvested for immunoassay testing of ALK and pY1586 ALK status. Alectinib versus vehicle ***, P = 0.0005. Lorlatinib versus vehicle. **, P = 0.0037. C, Th-ALKF1174L/MYCN animals were treated with lorlatinib BD versus vehicle control to assess survival. ****, P < 0.0001 according to log-rank (Mantel–Cox) test. D, Tumor volume was monitored by MRI. E, Representative abdominal MRI of an animal from the lorlatinib survival study versus vehicle control. Tumor outlined by white line.

Lorlatinib treatment of Th-ALKF1174L/MYCN tumor-bearing animals gives a survival advantage over vehicle control. A,In vivo analysis of a panel of ALK inhibitors including crizotinib, ceritinib, alectinib, and lorlatinib was carried out using the Th-ALKF1174L/MYCN model. Tumor-bearing Th-ALKF1174L/MYCN mice, were treated with the indicated inhibitor or its corresponding vehicle (veh.) over a 3-day interventional dosing schedule, and tumor volume change was monitored by MRI on day 0 and day 3. Each bar represents tumor volume change in an individual animal. Crizotinib versus vehicle ****, P < 0.0001. Alectinib versus vehicle **, P = 0.0021. Lorlatinib versus vehicle ***, P = 0.0002. B, Tumors from A were harvested for immunoassay testing of ALK and pY1586 ALK status. Alectinib versus vehicle ***, P = 0.0005. Lorlatinib versus vehicle **, P = 0.0037. C, Th-ALKF1174L/MYCN animals were treated with lorlatinib twice daily versus vehicle control to assess survival. ****, P < 0.0001 according to log-rank (Mantel–Cox) test. D, Tumor volume was monitored by MRI. E, Representative abdominal MRI of an animal from the lorlatinib survival study versus vehicle control. Tumor outlined by white line.