Trastuzumab deruxtecan gives strong anti-tumour activity and durable responses in multiple tumour types

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Published: 5 Jun 2023
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Dr Funda Meric-Bernstram - MD Anderson Cancer Center, Houston, USA

Dr Meric-Bernstam talks to ecancer at ASCO 2023 about data she presented on trastuzumab deruxtecan, a HER2-targeted antibody drug conjugate.

Encouraging responses and long-lasting clinical benefit in several tumour types was observed in the phase II DESTINY-PanTumor02 study.

Treatment achieved an objective response rate of 61.3% with a median duration of response of 22.1 months in patients with the highest levels of HER2 expression.

Across all patients, the overall response rate (ORR) was 37.1% with a median DOR of 11.8 months. An ORR of more than 30% was observed in all cancer types except biliary tract (22%) and pancreatic cancers (4%).

Across different disease sites, trastuzumab deruxtecan resulted in the following ORRs:

  • Endometrial cancer: 57.5% for all patients, 84.6% for IHC 3+, and 47.1% for IHC 2+
  • Cervical cancer: 50% for all patients, 75% for IHC 3+, 40% for IHC 2+
  • Ovarian cancer: 45% for all patients, 63.6% for IHC 3+, 36.8% for IHC 2+
  • Urothelial cancer: 39% for all patients, 56.3% for IHC 3+, 35% for IHC 2+
  • Biliary tract cancer: 22% for all patients, 56.3% for IHC 3+, 0% for IHC 2+
  • Pancreatic cancer: 4% for all patients, 0% for IHC 3+, 5.3% for IHC 2+

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I had the pleasure at ASCO 2023 to talk about the DESTINY-PanTumor02 interim results. This study looked at trastuzumab deruxtecan’s anti-tumour efficacy and safety across patients with advanced solid tumours that were HER2 expressing.  It’s a well-established antibody-drug conjugate that is quite potent. We know that this antibody-drug conjugate already has anti-tumour efficacy in HER2 expressing breast cancers, both HER2 low as well as HER2 positive breast cancers, and in HER2 positive gastric cancers, as well as HER2 mutant lung cancer. 

However, we also know that HER2 is expressed across a variety of tumour types and there are no approved treatment options for the other tumour types, thus there's an unmet clinical need. Further, when T-DXd was in clinical trials in early phase, there was a signal of activity already in multiple tumour types, including papillary tumours, salivary tumours and endometrial cancer. So this phase II trial looked at the at the anti-tumour efficacy of trastuzumab deruxtecan in a patient population that was advanced, selected for HER2 expression. 

We selected patients that had HER2 2+ or 3+ on IHC and we used either a central test or a local test for enrolment. We looked at six different tumour types. We looked at patients in three gynaecological cohorts: cervical cancer, endometrial cancer, ovarian cancer, at 2 GI cohorts: biliary and pancreatic cancer, and also a bladder cancer cohort. Then we had an all-comer solid tumour cohort that excluded these diseases and we enrolled patients that also excluded breast, gastric, colon and lung cancer. 

So we were very pleased at the analysis to see that of the 276 patients enrolled, by investigator assessment the objective response rate was 37%. These were durable responses with a median duration of response of 11.8 months. When we looked across tumour types, there are multiple tumour types where we see drug activity with an objective response rate that was quite high, especially in gynaecological cohorts, but also quite clinically meaningful in bladder cancer and biliary cancer.

The one disease we had less activity was in pancreatic cancer but there was significant stable disease and by central assessment of the responses there was a 12% objective response rate in that cohort. 

We also had done a central IHC assessment, so confirming the expression level centrally of patients that had high levels of HER2 expression, HER2 3+. Objective response rates were very high – in the overall 3+ population it was 61%. In the majority of the tumour cohorts it was over 50%. 

It was notable that the one disease type where we didn't have as much activity in pancreatic cancer, we only had two patients that were HER2 3+. Also notable was that our overall patient population duration of response was 11.8 months; within patients that were 3+ it was 22.1 months. 

The safety profile in the study was similar to what we already know. The main take home message is the study suggests T-DXd is active in HER2 expressing cancers across tumour types and may represent a new treatment option.