Top Abstracts from ASCO 2022

Notable research chosen by Cleveland Clinic Cancer Center staff

As we work together to deliver world-class cancer care, many in the oncology field look to the latest research discoveries shared each year at the American Society of Clinical Oncology’s annual meeting to improve the lives of patients. The staff of Cleveland Clinic Cancer Center is highlighting the 10 below abstracts as some of the most notable in terms of clinical significance and potential for practice improvements.

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1. Breast cancer

Destiny Breast04

The Destiny Breast04 trial evaluated the HER2-directed antibody-drug conjugate trastuzumab-deruxtecan (TDXd) in the treatment of refractory, HER2-negative metastatic breast cancer that had low levels of HER2-expression defined as 1+ or 2+ by immunohistochemistry. Compared with standard chemotherapy, TDXd was associated with an approximate doubling of time to progression and, even more impressively, over a six-month improvement in survival.

2. Lymphoma

First-line brentuximab vedotin plus chemotherapy to improve overall survival in patients with stage III/IV classical Hodgkin lymphoma: An updated analysis of ECHELON-1

For patients with advanced-stage Hodgkin lymphoma, the randomized ECHELON-1 trial compared standard ABVD x six cycles vs. a regimen in which bleomycin was replaced by the antibody drug conjugate brentuximab vedotin in combination with A+AVD. The study demonstrated a progression-free survival benefit. In addition, with longer follow-up reported at ASCO 2022, the study demonstrates a statistically significant improvement in overall survival. This data indicates that A+AVD should become the new standard of care for most patients with advanced-stage Hodgkin lymphoma. ABVD remains standard for early-stage disease.

3. Bone Marrow Transplant

Pre-MEASURE: Multicenter evaluation of the prognostic significance of measurable residual disease testing prior to allogeneic transplantation for adult patients with acute myeloid leukemia in first remission

In this retrospective study, the investigators assessed pre-allogeneic hematopoietic cell transplantation (alloHCT) measurable residual disease (MRD) by next-generation sequencing in >400 patients with available peripheral blood samples immediately prior to alloHCT. The presence of MRD was prognostic across multiple groups, with key findings that could influence both choice of whether to proceed to alloHCT at this time point in certain patients and/or alteration in conditioning regimens with the planned alloHCT.

4. Neuro-Oncology

Phase II randomized study comparing proton craniospinal irradiation with photon involved-field radiotherapy for patients with solid tumor leptomeningeal metastasis

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In this trial, patients who received proton craniospinal irradiation had a significant benefit in CNS progression-free survival (7.5 vs. 2.0 mo) and overall survival (8.2 vs. 4.9 mo), with very good tolerance. Patients with leptomeningeal metastasis and good performance status have the potential to gain meaningful benefit from proton craniospinal irradiation.

5. Lung Cancer

KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in patients with advanced/metastatic non-small cell lung cancer harboring a KRASG12C mutation

There is a large subset of patients with non-small lung cancer (13%) who have KRASG12C mutations, and adagrasib had significant activity in previously treated patients with KRASG12C. This will likely lead to the drug becoming approved as a new option for these patients. Sotorasib was already approved in 2021 for this indication. However, there was intriguing data presented at ASCO 2022 suggesting adagrasib was active in patients with brain metastases. This might make adagrasib a more appealing option.

6. Head and Neck Cancer

A Phase 2 trial of pembrolizumab and cabazantinib in patients with recurrent metastatic head and neck squamous cell carcinoma

This is the first abstract reporting results for combination therapy with an immune checkpoint inhibitor and VEGF inhibitor. This combination therapy is being evaluated in multiple H/N studies, and may prove a challenger to frontline standard therapy of chemo-immunotherapy.

7. Colorectal Cancer

Adjuvant chemotherapy guided by circulating tumor DNA analysis in stage II colon cancer: The randomized DYNAMIC trial

This study is one of the first to employ the use of circulating tumor DNA (ctDNA) in a randomized trial as a way to reduce use of adjuvant chemotherapy in patients with stage II colorectal cancer. The findings demonstrate that adjuvant therapy is quite beneficial in patients with positive ctDNA results, and also that some patients may be spared adjuvant chemotherapy if they are determined to be low risk. 

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8. Melanoma

Germline predisposition in oncologic and dermatologic melanoma cohorts

This comprehensive study of a prospectively accrued familial registry, along with analysis of three large multicenter retrospective datasets, demonstrates that the incidence of germline predisposition to cancer in individuals with melanoma ranges from 10.6-15.8%. These unexpectedly high rates are likely to change guidelines for melanoma management in favor of evaluating all patients with melanoma for a family history of cancer, and evaluating a large number of these patients for germline genetic testing.

9. Genitourinary Cancer

Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with Bacillus Calmette-Guérin (BCG) in BCG-unresponsive CIS and papillary non-muscle-invasive bladder cancer

This Phase 2/3 study evaluated the IL-15 superagonist N-803 in combination with BCG in previously BCG-unresponsive bladder cancer. In cohort A (CIS +/- papillary tumors), the complete response rate to BCG + N=803 was 71%, with a median duration of response of more than two years. Only 16% of patients went on to cystectomy, and 100% of patients were alive despite their bladder cancer diagnosis at the data cut-off.

10. Genitourinary Cancer

Long-term outcomes in EV-301: 24-month findings from the Phase 3 trial of enfortumab vedotin vs. chemotherapy in patients with previously treated advanced urothelial carcinoma

The EV-301 trial continues to show significant and consistent survival advantage over standard chemotherapy in patients with treatment-experienced locally advanced or metastatic urothelial cancer.