. 2023 Jun 1;4(8):100534. doi: 10.1016/j.jtocrr.2023.100534

Table 2.

Treatment Outcomes on ALK Plus MET-Directed Therapy and Longitudinal Biopsy Findings

Patient	ALK/MET Therapy	Best Response Time on Treatment	Pre-ALK/MET-Targeted Therapy Biopsy Findings	Post-ALK/MET-Targeted Therapy Biopsy Findings
1	Crizotinib 250 mg BID	PD <1 mo	MET/CEP7 ≥ 25, TP53 R273C, TP53 Q192∗, SETD2 V2280fs∗89	N/A
2	Crizotinib 250 mg BID	PR (−38%) 3.5 mo	MET/CEP7 ≥ 25, TSC2 D1612N, TP53 A161T	MET/CEP7 > 25, insufficient tissue for NGS
3	Lorlatinib 75 mg QD^a + crizotinib 250 mg BID	PR (−30%) 3 mo	MET/CEP7 5.7, ATM S378G, MDM4 splice region variant, ARID1A D1193N, PIK3CA E453K	MET/CEP7 > 25, ATM S378G, MDM4 splice variant, ARID1A D1193N, PIK3CA E453K
4	Lorlatinib 50 mg QD + crizotinib 250 mg BID	PD <1 mo	MET/CEP7 2.4, NF1 G2379R, TP53 V274G, MYC gain	MET/CEP7 > 25, NF1 G2379R, TP53 V274G, NOTCHL1 S2364G, MYC gain
5	Lorlatinib 50 mg QD^a + crizotinib 250 mg BID	PR (−60%) 11 mo^b	MET/CEP7 ≥ 25, APC Y1642_V1644del	N/A
6	Lorlatinib 50 mg QD + crizotinib 250 mg BID	PD <1 mo	MET/CEP7 5.5, TP53 R273C	N/A
7	Lorlatinib 50 mg QD + crizotinib 250 mg BID	PR (−51%) 6 mo	MET amplification (2.5), TP53 E346∗, MYC amplification (3.8) by plasma	MET amplification (6.8), TP53 E346∗, MYC amplification (19), MET L329fs (0.01) by plasma
8	Lorlatinib 50 mg QD + crizotinib 250 mg BID	PD <1 mo	MET amplification (5.4), TP53 C135F (4.6), BRCA2 D3188fs (2.4), APC M314T (0.6), STK11 A43V (0.3)	MET amplification (20.6), BRCA2 D3188fs (9.1), TP53 C135F (25.6), ST7-MET (0.7), APC M314T (0.4), CDK12 P670A (0.3)
9	Alectinib 600 mg BID^a + capmatinib 400 mg BID	SD (non-CR/non-PD) 9 mo	MET/CEP7 ≥ 25, SMARCA4 P47T, EGFR P596L	(1) MET/CEP7 0.9, SMARCA4 P47T, EGFR P596L^c (2) MET/CEP7 2.3, ALK G1202R, SMARCA4 P47T, EGFR P596L^c
10	Alectinib 600 mg BID + capmatinib 400 mg BID^a	SD (−8%) 10 mo	MET/CEP7 ≥ 25, TP53 E180∗, APC E1156K	MET/CEP7 1.0, NF1 H1748Y, BRCA1 C328Y, TP53 E171K, PIK3CA E545K, MYC S160L, MYC S206L
11	Alectinib 600 mg BID + capmatinib 300 mg BID	PR (−70%) 7 mo	MET/CEP7 7.7, TP53 N131Y, SMARCA4 D1183N	N/A
12	Alectinib 600 mg BID + crizotinib 200 mg BID	SD (−26%) 6 mo	MET amplification by NGS, TP53 E285K	MET amplification by NGS, TP53 E285K

QD, daily; BID, twice daily; PD, progressive disease; PR, partial response; SD, stable disease; CR, complete response per RECIST v.1.1; N/A, not applicable, as no biopsy was performed; NGS, next-generation sequencing; CEP7, centromeric probe 7; RECIST, Response Evaluation Criteria in Solid Tumors.

Lorlatinib initially given at 50 mg and then escalated to 75 mg after 2 weeks for patient 3, lorlatinib reduced to 25 mg for neurocognitive toxicity for patient 5, alectinib escalated to 900 mg BID for patient 9 for brain progression, at which time capmatinib reduced to 300 mg BID, capmatinib reduced to 200 and 300 mg BID from 400 mg BID for patient 10 for pyrexia.

Treatment stopped for toxicity despite ongoing partial response.

Patient underwent resection and molecular analysis of two separate enlarging brain metastases.