Addition of Trastuzumab to Perioperative Chemotherapy Improved Response Rates Among Patients with HER2-Positive Gastric or Gastroesophageal Junction Cancer

Results From the EORTC 1203 INNOVATION Trial

At the 2023 World Congress on Gastrointestinal Cancers, Anna Wagner, MD, Department of Oncology, University of Lausanne, Switzerland, shares results from a trial evaluating the addition of trastuzumab, with or without pertuzumab, to perioperative chemotherapy for patients with HER2-positive gastric or gastroesophageal junction cancer.

Dr Wagner concluded, "The addition of trastuzumab to chemotherapy for HER2-positive patients with gastric cancer improved major pathologic response rate and survival rates are still pending."

Transcript:

My name is Anna-Dorothea Wagner from Lausanne University Hospital and the University of Lausanne. I'm a senior lecturer and consultant and head of the GI Cancer Clinic in the Department of Oncology at the University Hospital of Lausanne. At this year's World GI Congress in Barcelona, I had the pleasure to present the EORTC-1203, the INNOVATION trial. This stands for Integration of Trastuzumab, with or without Pertuzumab, into Perioperative Chemotherapy of HER2-Positive Gastric Cancer.

The background for this trial is that despite all progress, which we have made in the last years, still 50% of the patients treated with a curative approach with stage II and III gastric cancer in Western countries die of their disease. We know since many years that about 10% to 20% of patients with gastric cancers are HER2-positive. Since the ToGA trial, which was published in 2010, we know that patients with HER2-positive gastric cancer benefit from adding trastuzumab to chemotherapy.

Now, this was more than 10 years ago. Since that time, we have a target. We have a treatment. We use it only for the patients when they undergo palliative treatment and not when we can cure them. This was something I wanted to change. Every medical oncologist knows that for patients with breast cancer, locally advanced disease, the addition of trastuzumab to locally advanced, HER2-positive breast cancer increases 5-year survival by more than 10%. The question is whether as well, in gastric cancer, we can improve survival in patients with HER2-positive locally advanced gastric cancer by adding HER2-targeted treatments.

We designed the "INNOVATION"-trial with 3 arms, one arm with chemotherapy alone, one arm with chemotherapy plus trastuzumab, and one arm with chemotherapy plus trastuzumab and pertuzumab. What is important is that the trial was designed in 2012/2013, when the chemotherapy backbone was cisplatin plus 5-FU. This was the standard on which we could agree upon after discussion with our colleagues in Korea. We started with cisplatin plus 5-FU as chemotherapy backbone. After the publication of the FLOT-4 trial, the chemotherapy backbone was changed to FLOT. Therefore, 50% of the patients included of this trial approximately were treated with cisplatin plus 5-FU, and 50% were treated with FLOT.

The results of this trial show that the patients in whom trastuzumab was added to chemotherapy, the second arm, had an important benefit in major pathologic response rate, which was the primary end point of this trial. Overall, the major pathologic response rates were 23% in the patients treated with chemotherapy alone. They were 37% in the patients treated with chemotherapy plus trastuzumab, and they were 27% in the patients treated with the double antibody combination.

Really, the patients who were treated with chemotherapy plus trastuzumab had an important benefit in term of major pathologic response rate by the addition of trastuzumab to chemotherapy. This benefit from the addition of trastuzumab to chemotherapy was most pronounced in the patients treated with FLOT as chemotherapy backbone. These patients had a 53% major pathologic response rate as compared to 33% major pathologic response rate in the patients treated with chemotherapy alone.

One major question is, why did the trial arm with the double-antibody combination perform so poorly? We have the answer to this question in the trial. This is probably due to toxicity-related reduced dose intensity of chemotherapy. Major toxicity from trastuzumab and pertuzumab, the double antibody combination, were diarrhea and mucositis. Patients treated with the double antibody combination could often not receive the 4 cycles of preoperative chemotherapy. While patients treated with chemotherapy alone, 93% of patients were able to get 4 cycles of FLOT. For example, before surgery in patients treated with the double-antibody combination, this figure dropped to 80%. About one-fifth of the patients could not receive all 4 cycles of chemotherapy. This had a major negative impact.

In conclusion, the addition of trastuzumab to chemotherapy for HER2-positive patients with gastric cancer improved major pathologic response rate and survival rates are still pending. I thank you for your attention.

Source:

Wagner A, Grabsch H, Mauer M, et al. Integrating trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy (CT) of HER-2+ gastric cancer (GC) – subgroup analyses of EORTC 1203 “INNOVATION”, a collaboration with KCSG and DUCG. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-5