ASCO update—best of the best

Dear colleagues,

For many of us, the “face to face” attendance at the most important meeting for medical oncologists and colleagues from several other disciplines related to clinical oncology, namely the ASCO annual meeting, was already a highlight by itself after numerous—in general also excellent—virtual meetings over the past 2 years during the coronavirus disease 2019 (COVID-19) pandemic. In spite of numerous challenges caused by the pandemic, it is noteworthy that several clinically important studies were performed and successfully finished during the pandemic. ASCO 2022 was characterized by three main topics: First, the success with the new generation of antibody drug conjugates (ADCs). Second, the transfer of the success of immune checkpoint inhibitor (ICI) therapy from the palliative setting into the adjuvant and neoadjuvant setting and third, de-escalation of therapy by using circulating tumor DNA (ct-DNA) measurements or replacing classical chemotherapy and radiotherapy with immunotherapy.

Trastuzumab deruxtecan (TDX-d) had already shown its superiority in “classical HER2-positive” breast cancer (BC) compared to trastuzumab emtansine (T-DM1) in patients who were previously treated with trastuzumab and taxane in the phase III DESTINY-Breast03 trial [1]. In the phase III DESTINY-Breast04 trial TDX‑d now demonstrated a significantly superior progression-free (PFS) and overall survival (OS) compared to physician’s choice in patients with previously treated “HER2 low” metastatic BC [2]. HER2 low was defined as immunohistochemical (IHC)1+, or IHC2+ and in situ hybridization (ISH) negative. These data will broaden the population of patients with metastatic BC who are candidates for a HER-directed therapy dramatically by about 50%! Other ADCs, like sacituzumab govitecan (SG) also showed superior OS in pretreated triple-negative BC compared to physician’s choice [3] and disitamab vedotin showed excellent response rates again not only in HER2/IHC3+ and HER2/IHC2+ positive patients but also in HER2 low (i.e., HER2/IHC2+ FISH negative) patients with locally advanced or metastatic urothelial carcinoma [4].

Immunotherapy, especially with ICIs is very strongly on the rise, not only in the palliative but also in the adjuvant and neoadjuvant setting. The presence of the tumor in the neoadjuvant situation may lead to higher numbers of tumor-resident T cell clones in the periphery after neoadjuvant therapy and subsequently to better outcome. This hypothesis is supported among others by the PRADO trial in stage IIIB/C de novo or recurrent melanoma patients who achieved pathologically complete or near-complete remission rates of 61% with ipilimumab and nivolumab [5]. A highlight of ICI therapy was a small but nevertheless groundbreaking study on 14 patients with mismatch repair (MR) deficient locally advanced rectal cancer that were treated with a single programmed death 1 (PD-1) blocking agent, namely dostarlimab, over 6 months [6]. All 14 patients (100%) achieved a clinically complete response and remained progression free for up to 14 months so far. This means that in this small population of MR-deficient patients with locally advanced rectal cancer chemotherapy, radiotherapy and surgery could be possibly omitted in the future. The effectiveness of ICI therapy in microsatellite-high (MSI-H) tumors or tumors with MR-deficiency with the PD1-inhibitor dostarlimab was also documented in the phase III GARNET study in advanced/metastatic endometrial cancer [7]. Patients with MSI‑H tumors or tumors with MR-deficiency showed a superior PFS and OS compared to patients with mismatch repair-proficiency or those with microsatellite-stable tumors.

Another important finding reported at the recent ASCO meeting was the de-escalation of chemotherapy by using circulating tumor DNA (ct-DNA) in order to avoid adjuvant chemotherapy in stage II colon cancer in the DYNAMIC trial [8]. This ct-DNA-guided strategy was able to halve the number of patients that received chemotherapy post surgery, while the chance of remaining alive and free of cancer at 3 years remained comparable.

Some of these data with more details as well as data on other entities such as hepatocellular carcinoma, cholangiocellular carcinoma, bladder cancer and central nervous system tumors will be presented in the following articles.

Conflict of interest

A. Petzer: Honoraria/advisory role: Novartis, Amgen, Celgene-BMS, Sandoz, Janssen, Astra Zeneca, AbbVie, Takeda, Sanofi, Kite-Gilead, Roche, Pfizer, Seagen, Daiichi Sankyo. Travel support: Janssen, Astra Zeneca, Kite-Gilead, Roche, Pfizer, Daiichi Sankyo.