New research was presented in this year’s ASCO 2020 Virtual Scientific Program, the annual meeting of the American Society of Clinical Oncology, from May 29-31.
Breast Cancer Brain Mets Treated With Tucatinib
The risk of death or progression of brain metastases was reduced in patients with HER2-positive advanced disease who received prior trastuzumab/ pertuzumab and T-DM1 when they added tucatinib to a regimen of trastuzumab and capecitabine, study investigators said. Patients who were treated with trastuzumab and capecitabine alone achieved a median overall survival of 12.0 months, but that survival was increased to 18.1 months with tucatinib on board. The median central nervous system progression-free survival was 9.9 months in the tucatinib-treated patients compared with 4.2 months among the patients getting trastuzumab and capecitabine alone.
The combined primary endpoint of death or progression of brain metastases was a 68% reduction in favor of tucatinib. Intracranial objective responses were observed in 47.3% of the patients on tucatinib compared with 20.0% on trastuzumab/capecitabine. At 1 year, 70% of patients randomized to tucatinib were alive, compared with 47% randomized to placebo. About 48% of patients had brain metastases at baseline, and among them, 60% had active brain metastases, meaning untreated brain metastases or progressing brain metastases.
Larotrectinib Produces Durable Responses
Patients diagnosed with a variety of advanced cancers appear to have durable responses when treated with larotrectinib, an agent that attacks tropomyosin receptor kinase (TRK) fusion pathology, researchers reported. Across three studies, patients were treated with 17 types of cancer, including thyroid (22%), salivary gland (19%), soft tissue sarcoma (16%), lung (12%), colon (7%), melanoma (5%), breast (5%), gastrointestinal stromal tumors (3%), and nine other types (≤ 2% each). About 78% of the patients had received prior systemic therapy and 68% had undergone two or more lines of therapy. More than 70% achieved either a complete (10%) or objective partial response. Overall, about 60% of patients also had an objective response and another 16% experienced disease stabilization with larotrectinib. The median duration of response for all adults in the study was 35.2 months, with some patients having responses that were durable through 51 months of therapy. Median progression-free survival was 25.8 months.
Consultant Palliation Improves AML Quality of Life
Referring a patient diagnosed with acute myeloid leukemia (AML) to the palliation service at the time grueling therapy begins appears to offer psychological benefits down the road, including improvements in the patients’ perceived quality of life, researchers found. For the study, patients with high-risk AML and admitted to receive intensive chemotherapy were randomized to integrated palliative and oncology care or usual care. Those receiving the intervention met with palliative care clinicians at least twice weekly. At 2 weeks—a period recognized as most difficult for patients who are in the midst of long-term hospitalization— the quality of life among patients who received palliation department consultation did not deteriorate, while patients who received standard of care experienced a decline of 8 points in the FACT-Leukemia scale. At 24 weeks, the quality of life improved in both arms of the trial, but by 25 points from baseline in patients who received an intervention, compared with 10 points in the patients receiving standard care.
Progression Free Survival Improved with Pembrolizumab for ES-SCLC But Not Overall Survival
Data from the phase III KEYNOTE-604 trial showed that although patients with extensivestage small cell lung cancer (ES-SCLC) who received pembrolizumab with backbone chemotherapy etoposide/platinum (EP) compared with patients who received EP and placebo did not benefit from improved overall survival (OS), progression-free survival (PFS) rates with the combination did reach the threshold for significance. The KEYNOTE-604 study aimed to improve upon the efficacy of immunotherapy in newly diagnosed ES-SCLC with the combination of pembrolizumab and EP. The study randomized 453 patients; pembrolizumab 220 mg on day 1 plus EP 100 mg/m2 on days 1 and 2 and carboplatin AUC 5 on day 1 or cisplatin 75 mg/m2 on day 1 or placebo, matching EP, and carboplatin or cisplatin for up to 31 cycles. The final PFS analysis was significant (4.8 vs 4.3 months; HR: 0.73; 95% CI: 0.60- 0.88).
The 12-month PFS rate observed with the pembrolizumab combination was 15.9% versus 5.0% with the placebo combination. Even at 18 months, the PFS rate in the pembrolizumab arm was higher than the placebo arm at 10.8% versus 2.1%. In terms of OS, pembrolizumab/EP prolonged OS compared with the control combination (10.8 vs 9.7 months; HR: 0.80), but it did not reach the superiority threshold. The 12-month OS rate was 45.1% in the pembrolizumab arm compared with 39.6% in the placebo arm. At 24 months, the OS rate was 22.5% in the pembrolizumab arm compared with 11.2% in the placebo arm. The safety analysis showed that adverse events (AEs) of any-grade occurred in 100% of patients in the pembrolizumab arm and 99.6% of patients in the placebo arm, in the as-treated population. AEs were grade 3/4 in 76.7% of subjects who received pembrolizumab/ EP compared with 74.9% of those who received the placebo combination. Grade 5 AEs/death occurred in 6.3% of patients in the pembrolizumab arm versus 5.4% in the control arm.
Survival Benefit Emerges in ARAMIS
Men diagnosed with non-metastatic castrationresistant prostate cancer live longer if they are treated with darolutamide than placebo, the final results of the phase III ARAMIS trial revealed, adding to previous reports from the study that it met its primary endpoint of metastasis-free survival and that darolutamide delays radiographic progression, slows time for the need of cytotoxic chemotherapy, and slows progression to pain and skeletal events. For the study, 1,509 men diagnosed with non-metastatic castration-resistant prostate cancer were treated with darolutamide 600 mg twice daily or placebo. All the patients continued androgen-deprivation therapy. About 15.5% of patients who were treated with darolutamide died, compared with 19.1% of those in the placebo group, a 31% relative risk reduction that achieved statistical significance. The drug was well tolerated, with some increases in fatigue reported but no increased risk of cognitive impairment, seizures, falls or fractures, hypertension, or rash.