Abstract 40P
Background
Lorlatinib is a third generation ALK inhibitor with marked efficacy in NSCLC. CTCAE-defined weight gain and dyslipidaemia has been reported in patients receiving lorlatinib in registrational trials. Lipid-lowering agents may interact with lorlatinib metabolism.
Methods
We conducted a single centre retrospective analysis of NSCLC patients receiving lorlatinib. The primary objective was to quantify weight gain and lipid profile changes in accordance with CTCAE v5.0. Extraction from electronic medical records was undertaken by authors. Mean relative dose intensity (RDI) was defined as % of full dose lorlatinib for duration of therapy. All analyses were descriptive. Patients without baseline weight recorded were excluded. The project was approved by the hospital service evaluation committee.
Results
43 patients were evaluable. 77% (n=33/43) were ALK+ and 23% (n=10/43) ROS1+. Mean duration of lorlatinib was 14.5 months. Mean RDI was 81%. Weight gain occurred in 81% (n=35/43) of patients, 44% (n=19/43) Grade≥1 and 9% (n=4/43) Grade≥3. Mean weight gain/BMI was 6.4kg/2.4kg/m2 (range 0-30.1kg/11.4kg/m2). Dietitian referral occurred in 5% (n=2/43). Increase in total cholesterol (TChol) occurred in 51% (n=22/43) and triglyceride in 58% (n=25/43) of patients. 84% (n=36/43) were prescribed statins and 2% (n=1/43) ezetimibe/statin. 35% (n=15/43) patients had normal baseline TChol (<5mmol/L), 100% (n=15/15) of whom developed elevated TChol on lorlatinib, 73% (n=11/15) within 30 days of commencement. One patient with elevated TChol (8.3mmol/l) developed acute coronary syndrome 5 weeks after stopping lorlatinib.
Table: 40P
Baseline characteristics
| Total; n=43 (%) | ||
| Median age | 55.5 years | |
| Sex | Male | 18 (42) |
| Female | 25 (58) | |
| Oncogene | ALK | 33 (77) |
| ROS1 | 10 (23) | |
| Treatment line | 1st | 0 (0) |
| 2nd | 14 (33) | |
| 3rd | 13 (30) | |
| 4th | 8 (19) | |
| 5th | 7 (16) | |
| 6th | 1 (2) | |
| Initial dose | 100mg | 40 (93) |
| 75mg | 2 (5) | |
| 50mg | 1 (2) | |
| Dose modifications | Yes | 21 (49) |
| No | 22 (51) | |
| Concomitant steroids | Yes: ≥2 weeks | 14 (33) |
| Yes: <2 weeks | 3 (7) | |
| No | 26 (60) | |
| Mean RDI | 81% | |
| Median duration on lorlatinib | 14.5 months | |
| Weight gain, n=43 (%) | ||
| Yes- maximum grade | | 16 (37) | |
| G1 (5-10%) | 10 (23) | |
| G2 (10-20%) | 5 (12) | |
| G≥3 (>20%) | 4 (9) | |
| No | 8 (19) | |
| Unknown | 1 (2) | |
| Cholesterol, n=43 (%) | ||
| TChol increase | Yes | 22 (51) |
| No | 21 (49) | |
| Mean increase | 1.94mmol/L | |
| Maximum grade of hypercholesterolaemia in pts with normal baseline TChol, n=15 (%) | G1 | 10 (67) |
| G2 | 4 (27) | |
| G3 | 1 (7) | |
| G4 | 0 |
Conclusions
Real world prevalence of weight gain was similar to that reported in landmark trials. Dyslipidaemia is frequent and requires active treatment which may impact metabolism of lorlatinib. Larger scale evaluation on quality of life impact and medical risk of weight gain/dyslipidaemia is required.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D.J. McMahon: Non-Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Sponsor/Funding, Educational travel: Pfizer, Takeda. D.D. Chauhan: Financial Interests, Personal, Invited Speaker: BMS, MSD. M. Davidson: Financial Interests, Personal, Invited Speaker: Takeda. A.R. Minchom: Financial Interests, Personal, Other, Expenses: Amgen pharmaceuticals, LOXO oncology; Financial Interests, Personal, Invited Speaker: Bayer Pharmaceuticals, Chugai Pharmaceuticls, GSK, Janssen Pharmaceuticals, Merck pharmaceuticals; Financial Interests, Personal, Advisory Board: Faron pharmaceuticals, Janssen Pharmaceuticals, Merck pharmaceuticals, Takeda, Genmab; Financial Interests, Personal, Expert Testimony: GSK; Financial Interests, Institutional, Other, Research funding: MSD, Merck Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Novartis Oncology. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Guardant Health, BeiGene, Takeda, Lilly, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Expert Testimony: Merck Serono, Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Invited Speaker: Ariad, AstraZeneca, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, GSK, Takeda, Trizel, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Personal, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Personal, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Personal, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Personal, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. All other authors have declared no conflicts of interest.