The live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting kicked off this morning with highlights sessions that captured some of the most important studies.
The gastrointestinal cancer session featured four studies, one of which was a phase 2/3 trial that compared donafenib to sorafenib in liver cancer. HER2CLIMB and MINDACT were both discussed during the breast cancer session. Although not discussed this morning, the results of PHERGAIN dropped at this meeting and offer a de-escalation strategy for patients with early breast cancer.
Patients with unresectable or metastatic hepatocellular carcinoma who received donafenib in the first-line setting lived a median of nearly two months longer than patients who received standard of care sorafenib (12.1 months vs 10.3 months), results showed in the open-label, randomized phase 2/3 trial (Abstract 4506).
Patients in the donafenib arm (n=334) also had a 17% reduced risk of death compared with the sorafenib arm (n=334; HR=0.831; 95% CI, 0.699 – 0.988; P=0.0363). However, no difference was seen between the donafenib arm and sorafenib arm for progression-free survival (PFS; 3.7 vs 3.6 months; P=0.2824), objective response rate (4.6% vs 2.7%; P=0.2448), and disease control rate (30.8% vs 28.7%; P=0.5532).
Donafenib appeared to have a better safety profile, with a significantly lower rate of drug-related adverse events that led to treatment interruption compared with sorafenib (25.2% vs 36.1%; P=0.0025). The donafenib arm also had a significantly lower rate of drug-related adverse events of grade 3 or higher (37.5% vs 49.7%; P=0.0018).
Marcus Noel, MD, associate professor of medicine, Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, cautioned that this study was conducted in China and is not an international study.
“Not sure if this is going to be able to extrapolate across the globe, but certainly donafenib has a place in first-line therapy, further pushing sorafenib to the side,” he said.
Tucatinib in combination with trastuzumab and capecitabine extended overall survival (OS) and delayed disease progression in the central nervous system (CNS) for patients with HER2-positive metastatic breast cancer and brain metastases, results showed from an exploratory efficacy analysis of the phase 2 HER2CLIMB trial (Abstract 1005).
Trial participants were randomly assigned to receive tucatinib in combination with trastuzumab and capecitabine (n=410) or placebo in combination with trastuzumab and capecitabine (n=202). The exploratory analysis included only patients with brain metastases at baseline, of which 291 of 612 (48%) randomized to treatment had.
Patients with brain metastases in the tucatinib arm had a 68% reduced risk of disease progression in the CNS compared with the placebo arm (HR=0.32; 95% CI, 0.22 – 0.48; P<0.0001) and a nearly 6-month gain in median CNS PFS (9.9 vs 4.2 months).
Patients in the tucatinib arm also had a 42% reduced risk of death compared with the placebo arm (HR=0.58; 95% CI, 0.40 – 0.85; P=0.005), and an approximately 6-months gain in overall survival (OS; 18.1 vs 12.0 months). The intracranial response rate more than doubled with tucatinib compared with placebo (47% vs 20%; P=0.03).
“HER2CLIMB serves as a wonderful story for the liberalization of clinical trial entry criteria and inclusion of patients that we need in clinical trials and who need novel therapeutics as well,” said Erika Hamilton, MD, Sarah Cannon.
A long-term analysis of the phase 3 MINDACT trial confirmed that the 70-gene signature MammaPrint assay can identify which breast cancer patients with a high clinical-pathological risk do not need adjuvant chemotherapy (Abstract 506).
Among the intention to treat population with a median follow-up of 8.7 years, patients with high clinical risk but low genomic risk who received adjuvant chemotherapy (n=749) had a small gain in distant metastasis-free survival (DMFS) compared with patients who did not receive chemotherapy (n=748; 92.0%; 95% CI, 89.6 – 93.8% vs 89.4%; 95% CI, 86.8 – 91.5).
A subgroup analysis among hormone-receptor positive and HER2-negative patients revealed no difference in DMFS between treatment groups for patients over the age of 50, yet a 5% difference for patients 50 years or younger, favoring treatment with chemotherapy (93.6%; 95% CI, 89.3% – 96.3% vs 88.6%; 95% CI, 83.5 – 92.3%).
“MINDACT showed us that patients with clinical high, genomic low disease continue to do well without chemotherapy at 8 years of follow-up,” said Angela de Michele, MD, University of Pennsylvania. She cautioned that the DMFS gain seen with chemotherapy for premenopausal patients “may be due to a lack of ovarian function suppressant in the non-chemotherapy arm.”
A PET/CT scan with fluorodeoxyglucose (FDG) tracer helped identify which patients with HER2-positive early breast cancer were most likely to benefit from trastuzumab and pertuzumab with endocrine therapy, according to the results of the PHERGAIN trial (Abstract 503).
Patients with HER2-positive disease were randomized to receive either trastuzumab and pertuzumab with chemotherapy (n=71) or trastuzumab and pertuzumab with endocrine therapy (n=285).
A PET/CT scan was used to guide treatment for patients in the chemotherapy-free arm by having patients undergo imaging after 6 weeks of treatment. If the scan showed a response, patients continued on the chemotherapy-free regimen. If not, patients switched to trastuzumab and pertuzumab with chemotherapy. Patients in the chemotherapy-containing arm also underwent imaging but the results were not used to guide treatment.
For the chemotherapy-free arm, patients who had a PET response achieved a higher pathologic complete response rate compared with patients who did not have a PET response (37.9% vs 25.9% P=0.069).
Study presenter Javier Cortes, MD, PhD, IOB Institute of Oncology, Hospital Quirónsalud, Medica Scientia Innovation Research, and Vall d’Hebron University of Oncology, said the chemotherapy-free strategy did not “jeopardize” breast conserving surgery and was also associated with a “more favorable” toxicity profile.
By Christina Bennett, MS
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