381P - Treatment rechallenge after grade 1 trastuzumab-deruxtecan related interstitial lung disease: A real-world experience

Background

Trastuzumab-deruxtecan (TDxd) is approved for advanced HER2+/low breast, gastric, and NSCLC cancers. TDxd has a rare, possibly serious risk of interstitial lung disease/pneumonitis (ILD; incidence 12-15%). For symptomatic ILD (≥G2), TDxd is permanently discontinued. For G1 ILD, TDxd is held with the option of rechallenge (RC) if ILD radiographically resolves. Limited data exist for outcomes of TDxd RC after G1 ILD.

Methods

We analyzed all pts treated with TDxd at our institution from 2018-2023. We identified pts with radiographic evidence of ILD by chart review. Adjudication of TDxd related ILD was by treating provider assessment and graded via CTCAE v5.

Results

Of 176 pts treated with TDxd, 29 (16%) developed ILD (18-G1, 7-G2, 1-G3, 1-G4, 2-G5). Median (med) ILD onset was 131 days (d) after 1st dose [range (r:) 29-512]. Among pts with ILD, 26 had breast and 3 had GI cancers, with a med age of 61 yrs (r: 39-79), med of 3 prior therapy lines for advanced disease (r: 1-13); 4/29 pts (14%) had renal impairment (CrCl<60mL/min). Among G1 ILD pts, 14/18 (78%) received steroids for a med of 44d (r: 14-124). Radiographic improvement was seen at a med of 23d (r: 9-79) for pts treated with steroids vs 47d (r: 28-81) without steroids. Fourteen of 18 pts (78%) with G1 ILD were RC with TDxd; 4 had disease progression. Two pts who did not receive steroids were RC. After RC, 10 pts remained on TDxd without recurrent ILD for a med of 100d (r: 20-306); 3 pts remain on TDxd at data lock (4/8/24); and 4 pts had recurrent ILD at a med of 148d after RC (r: 47-273; 3-G1, 1-G2). Two with recurrent G1 ILD were RC a 2nd time (1 dose reduced) and remained on TDxd until disease progression (63d and 211d). To evaluate for radiographic resolution/improvement of ILD, data from an ongoing blinded radiology review of all CT scans will be reported.

Conclusions

The rate of TDxd associated ILD in this analysis is similar to prior reports (16% all grade, 1% G5). Most cases were G1, treated with steroids, and were RC after ILD improvement. After RC, pts remained on TDxd for a med of 100d. Only 4/14 pts had recurrent ILD, all were G1-2, and 2 pts were RC a 2^nd time. This cohort provides clinically important information on RC safety and optimal use of TDxd; understanding CT scan resolution/improvement is a key factor.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S.C. Behr: Financial Interests, Personal, Advisory Role: GenVivo, Advanced Accelerator Applications, MORE Health, Progenics; Financial Interests, Personal, Other, Honoraria: University of Texas Medical Branch at Galvaston; Financial Interests, Personal and Institutional, Research Funding: Cancer Targeted Technology. L. Quintal: Financial Interests, Personal, Advisory Role: AstraZeneca. J. Chien: Financial Interests, Institutional, Research Funding: Merck, Puma Biotechnology, Seagen, Amgen. M.E. Melisko: Other, Personal, Speaker’s Bureau, via an Immediate Family Member: Genentech, AstraZeneca; Other, Personal, Advisory Board, via Immediate Family Member: Gilead Sciences; Financial Interests, Personal, Expert Testimony: GSK; Financial Interests, Personal, Proprietary Information, Multiple patents related to immunoliposomal drugs being studied and potentially brought to market by Merrimack via an immediate family member.: Merrimack; Financial Interests, Personal, Stocks or ownership, via an immediate family member: Merrimack; Financial Interests, Institutional, Research Funding: Novartis, DAEHWA Pharmaceutical, OBI Pharma. A.H. Ko: Financial Interests, Personal, Other, Member of Data Monitoring Committee: Roche/Genentech, Grail; Financial Interests, Personal, Other, Chair of Pancreatic Cancer Task Force: National Cancer Institute; Financial Interests, Personal, Invited Speaker, Invited speaker x 1: Medscape, Research to Practice; Financial Interests, Personal, Invited Speaker, Invited speaker x 2: OncLive (MJH Life Sciences); Financial Interests, Personal, Advisory Board, Advisory board x 1: Genentech, Aadi, Merus, Eisai, Arcus; Financial Interests, Personal, Other, Advisory board x 1; invited speaker x 2: Fibrogen; Financial Interests, Institutional, Local PI, Local PI for clinical trial (esophageal cancer): Bristol Myers Squibb; Financial Interests, Institutional, Local PI, Local PI for clinical trial (gastric cancer): Leap Therapeutics, Astellas; Financial Interests, Institutional, Coordinating PI, National PI for clinical trial (GI cancers): Abgenomics; Financial Interests, Institutional, Coordinating PI, National PI for clinical trial (esophageal cancer): Apexigen; Financial Interests, Institutional, Other, National PI for clinical trial (pancreatic cancer): Crystal Genomics; Financial Interests, Institutional, Local PI, Local PI for clinical trial (pancreatic cancer): Verastem, Genentech; Non-Financial Interests, Other, MemberMultiple prior committee/speaking roles for Annual MeetingAssociate Editor: American Society of Clinical Oncology; Non-Financial Interests, Sponsor/Funding, For Precision Promise clinical trials consortium. Funding paid directly to my institution.: Pancreatic Cancer Action Network; Non-Financial Interests, Sponsor/Funding, For clinical trials collaboration. Funding paid directly to my institution.: Parker Institute for Cancer Immunotherapy. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc.; Financial Interests, Institutional, Coordinating PI: OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. All other authors have declared no conflicts of interest.