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ESMO 2023 Highlights

CE / CME

Key Studies in Breast, Lung, Gastrointestinal, Genitourinary, and Skin Cancers: CCO Independent Conference Highlights of the 2023 ESMO Congress

Physician Assistants/Physician Associates: 1.50 AAPA Category 1 CME credits

Nurses: 1.50 Nursing contact hours

Physicians: maximum of 1.50 AMA PRA Category 1 Credits™

Pharmacists: 1.50 contact hours (0.15 CEUs)

Released: December 22, 2023

Expiration: December 21, 2024

Natasha Leighl
Natasha Leighl, MD, MMSc, FRCPC, FASCO
Evan J. Lipson
Evan J. Lipson, MD
John Marshall
John Marshall, MD
Joyce O'Shaughnessy
Joyce O'Shaughnessy, MD
Daniel P. Petrylak
Daniel P. Petrylak, MD
CME/CE Information

Activity

Progress
1
Course Completed

Trastuzumab Deruxtecan for Treatment of Solid Tumors With HER2 Mutations

Natasha Leighl, MD, FRCPC, FASCO:
Fam-trastuzumab deruxtecan-nxki (T-DXd) has received accelerated approval for adult patients with unresectable or metastatic NSCLC harboring activating HER2 mutations who have received a prior systemic therapy.[Fam-trastuzumab deruxtecan-nxki PI] T-DXd also has several approved indications in breast cancer and is approved for patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma after a prior trastuzumab-based regimen.

A phase I study suggested efficacy for T-DXd in patients with various solid tumors with HER2 mutations or HER2 overexpression with an ORR of 47.4%.[Tsurutani 2020] 

DESTINY-PanTumor01: T-DXd in Patients With HER2-Activating Mutations in Solid Tumors

Natasha Leighl, MD, FRCPC, FASCO:
Data from the open-label, single-arm phase II DESTINY-PanTumor01 study were presented at ESMO 2023.[Li 2023] Patients with unresectable or metastatic solid tumors harboring HER2 mutations (N = 102) who had progressed on previous therapy received 5.4 mg/kg T-DXd. The study looked at a range of prespecified HER2 mutations, including those from the extracellular, transmembrane/juxtamembrane, and kinase domains.
The primary endpoint was confirmed ORR by independent central review, with secondary endpoints including DoR, disease control rate, confirmed ORR by investigator, PFS, OS, and safety.

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DESTINY-PanTumor01: Baseline Characteristics

Natasha Leighl, MD, FRCPC, FASCO:
This was a heavily pretreated population with a median of 3 prior therapies, and 56.9% of the patients had received ≥3 prior therapies.[Li 2023] Various tumor types were represented, including breast (19.6%), colorectal (19.6%), and biliary tract (18.6%), among others. Approximately one half of the patients’ HER2 mutations were located within the kinase domain.

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DESTINY-PanTumor01: Efficacy

Natasha Leighl, MD, FRCPC, FASCO:
The confirmed ORR was 29.4% (95% CI: 20.8%-39.3%), which is a bit less than the activity we see in HER2-mutant lung cancer with T-DXd.[Li 2023; Li 2022; Goto 2023] The median DoR was not yet reached, and the median PFS of 5.4 months (95% CI: 2.7-7.1) and median OS of 10.9 months (95% CI: 8.3-14.9) were not yet mature. As seen in the other DESTINY trials, HER2 expression level did not predict response to T-DXd.

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DESTINY-PanTumor01: Safety

Natasha Leighl, MD, FRCPC, FASCO:
Toxicity was very similar to what we have seen before.[Goto 2023; Li 2023] In particular, interstitial lung disease or pneumonitis occurred in 10.8% of patients but was severe (grade ≥3) in only 2.9% of patients. Another 2.9% of patients had a grade 1-2 decrease in left ventricular ejection fraction. 

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DESTINY-PanTumor01: Clinical Implications

Natasha Leighl, MD, FRCPC, FASCO:
I think this study is very interesting, as it clearly shows how different targetable alterations, such as HER2 mutations, can be found in many tumor types. There is the potential for HER2-targeted therapy for patients with a broader range of tumor types other than lung, breast, and gastric cancer, where T-DXd is currently indicated. The response rate of 29.4% seen in this study is across multiple tumor types and is lower than that seen in patients with HER2-mutant NSCLC.[Li 2022; Goto 2023] This likely speaks to the fact that the type of cancer is still important in addition to the genomic profile. 

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