Ahead of this weekend’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, late-breaking data dropped for three potentially practice-changing studies that will be presented during Sunday’s Plenary Session: JAVELIN Bladder 100, KEYNOTE-177, and ADAURA.
The addition of avelumab to best supportive care (BSC) in the maintenance setting appeared to benefit patients with unresectable advanced urothelial carcinoma who had received first-line platinum-based chemotherapy, according to an interim analysis of the phase 3 JAVELIN Bladder 100 trial (Abstract LBA1).
At median follow-up of approximately 19 months, overall survival (OS) was significantly longer for patients who received avelumab plus BSC (n=350) compared with BSC alone (n=350; HR=0.69; 95% CI, 0.56-0.86; P=0.0005). This benefit was seen across all subgroups. Patients with PD-L1–positive tumors also had significantly prolonged OS with avelumab plus BSC compared with BSC alone (HR=0.56; 95% CI, 0.40-0.79; P=0.0003).
Progression-free survival (PFS) was significantly longer for patients who received avelumab plus BSC compared with BSC alone (HR=0.62; 95% CI, 0.52-0.75; P<0.001), including those with PD-L1–positive tumors (HR=0.56; 95% CI, 0.43-0.73).
Patients who received avelumab plus BSC had a higher frequency of any grade (98.0% vs 77.7%) or grade 3 or higher (47.4% vs 25.2%) adverse events (AEs) compared with BSC alone. Common grade 3 or higher AEs for both arms were urinary tract infection, anemia, hematuria, fatigue, and back pain, all of which occurred at similar frequencies between arms.
Study presenter Thomas Powles, MD, Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, described the safety profile of avelumab as “in line” with other immune checkpoint inhibitors in this setting.
“Overall, avelumab first-line maintenance therapy in patients whose disease has not progressed with platinum-based induction chemotherapy is a new first-line standard of care for advanced urothelial cancer,” said Dr. Powles.
Pembrolizumab showed superior PFS compared with chemotherapy in patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer, meeting the primary endpoint of the phase 3 KEYNOTE-177 trial (Abstract LBA4).
At median follow-up of approximately 28 months, median PFS was more than 8 months longer for the pembrolizumab arm (n=153) compared with the chemotherapy arm (n=154; 16.5 vs 8.2 months), with a 40% reduction in risk of disease progression (HR=0.60; 95% CI, 0.45-0.80; P=0.0002).
At one year, PFS was higher for the pembrolizumab arm compared with the chemotherapy arm (55.3% vs 48.3%), which remained at 2 years (37.3% vs 18.6%). The overall response rate was also higher for the pembrolizumab arm compared with the chemotherapy arm (43.8% vs 33.1%), as was the complete response rate (11.1% vs 3.9%).
Pembrolizumab appeared to have a better safety profile, eliciting a lower frequency of grade 3 or higher AEs than chemotherapy (22% vs 66%). Also, no treatment-related deaths were reported for the pembrolizumab arm, while one was reported for the chemotherapy arm.
Study presenter Thierry Andre, MD, Sorbonne University and Saint-Antoine Hospital, described the PFS improvement seen with pembrolizumab as “clinically meaningful” and said pembrolizumab should be the “new standard of care” for this patient population.
Adjuvant osimertinib showed significantly improved disease-free survival (DFS) compared with placebo for patients with EGFR-mutation–positive NSCLC in the phase 3 ADAURA trial (Abstract LBA5).
The trial included 682 patients with stage IB to IIIA EGFR-mutation–positive NSCLC who were randomized to receive adjuvant osimertinib (n=339) or placebo (n=343) after complete tumor resection. Patients were given the option of having adjuvant chemotherapy before the assigned treatment.
The trial met its primary endpoint, showing an 83% reduction in risk of disease for patients with stage II to IIIA disease who received adjuvant osimertinib compared with placebo (DFS HR=0.17; 95% CI, 0.12 – 0.23; P<0.0001). The osimertinib arm had a 2-year DFS rate of 90% and placebo 44%.
When stage IB patients were included in the analysis, the osimertinib arm had a 79% reduction in risk of disease recurrence (DFS HR=0.21; 95% CI, 0.16 – 0.28; P<0.0001), with a 2-year DFS rate of 89% for osimertinib and 53% for placebo.
Common AEs seen with osimertinib were diarrhea (46%), paronychia (25%), dry skin (23%), and pruritis (19%), all of which were higher than those receiving placebo. No reported AEs with osimertinib lead to death. Overall, 3% of patients who received osimertinib developed interstitial lung disease and 7% QTc prolongation.
“Adjuvant osimertinib is the first targeted agent in a global randomized trial to show statistically significant and clinically meaningful improvement disease-free survival in patients with stage IB to IIIA EGFR-mutation–positive non-small cell lung cancer,” said study presenter, Roy Herbst, MD, PhD, Yale School of Medicine and Yale Cancer Center.
By Christina Bennett, MS
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