Top news of the week in oncology and cancer drug development.
Nab-Paclitaxel/Carboplatin Doublet Superior in Phase II tnAcity Trial
The combination of nab-paclitaxel and carboplatin reduced the risk of progression or death by 40% compared with 2 other chemotherapy doublets as a frontline therapy for patients with metastatic triple-negative breast cancer. The median progression-free survival was 7.4 months with nab-paclitaxel plus carboplatin compared with 5.4 months for nab-paclitaxel plus gemcitabine (HR, 0.60; 95% CI, 0.39-0.93; P = .02) and 6.0 months for gemcitabine plus carboplatin (HR, 0.61; 95% CI, 0.39-0.94; P = .03).
The 12-month PFS rate was 27% with nab-paclitaxel/carboplatin compared with 13% and 11% for nab-paclitaxel/gemcitabine and gemcitabine/carboplatin, respectively.
Pembrolizumab/Eribulin Combo Shows Promise for TNBC
The combination of pembrolizumab and eribulin demonstrated a 33.3% objective response rate for patients with metastatic triple-negative breast cancer who received 0 to 2 prior lines of therapy. In the open-label study, the ORR with the combination for untreated patients with metastatic TNBC (n = 17) was 41.2% (95% CI, 19.3-62.8).
In a cohort of patients pretreated with 1 to 2 therapies (n = 22), the ORR was 27.3% (95% CI, 11.3-46.4). PD-L1 status did not appear to impact results and toxicities were in line with expectations.
Pembrolizumab Shows Durable Responses in Heavily Pretreated TNBC
Treatment with pembrolizumab continued to show a consistent durable benefit with an additional year of follow-up for heavily pretreated patients with recurrent PD-L1-positive metastatic triple-negative breast cancer. In the updated findings, the median follow-up was 10.7 months and 2 patients had finished a complete 24-month course of pembrolizumab.
The median progression-free survival was 1.9 months (95% CI, 1.6-5.5) and the 12-month PFS rate was 17.8%. The median overall survival was 11.3 months (95% CI, 5.3-18.2) and the 12-month OS rate was 47.1%.
Everolimus Added to Fulvestrant Doubles PFS in HR+ Breast Cancer
The addition of everolimus to fulvestrant significantly improved progression-free survival in postmenopausal patients with metastatic HR—positive, HER2-negative breast cancer who are resistant to aromatase inhibitor therapy, according to findings from the phase II PrECOG 0102 trial.
In the study, the everolimus/fulvestrant combination doubled median PFS rates compared with fulvestrant alone, from 5.1 months on fulvestrant to 10.4 months with the combination (HR, 0.60; 95% CI, 0.40-0.92; P = .02).
World Conference on Lung Cancer
Durvalumab Provides Durable Response in Heavily Pretreated NSCLC
Durvalumab treatment in the second-line setting or beyond demonstrated clinical benefit and led to durable responses in heavily pretreated patients with locally advanced or metastatic non-small cell lung cancer.
The objective response rate with durvalumab increased in line with PD-LI expression: In PD-L1 low or negative patients with PD-L1 expression on less than 25% of tumor cells, the ORR was 7.5% (95% CI, 3.1—14.5), and ORR was 16.4% (95% CI, 10.8–23.5) in patients with PD-L1 expression ≥25%. But the highest ORR of 30.9% (95% CI, 20.2–43.3) was observed in patients with tumoral PD-L1 expression on ≥90% of tumor cells.
One-year overall survival rates were 48% in patients with PD-L1 ≥25% and 51% in patients with PD-L1 ≥90%. The relevance of the trial, in the context of pembrolizumab, nivolumab, and atezolizumab was questioned. Is another PD-1/PD-L1 inhibitor needed?
Atezolizumab Improves Survival in Second-Line NSCLC
Treatment with the PD-L1 inhibitor atezolizumab significantly improved overall survival (OS) compared to standard chemotherapy in patients with non—small lung cancer who progressed on platinum-based chemotherapy, according to results from the phase III OAK trial. OS in the intent-to-treat population (a co-primary endpoint of the OAK study) was 13.8 months in patients treated with atezolizumab (n = 425) versus 9.6 months in patients who received docetaxel (n = 425; HR, 0.73; 95% CI, 0.62-0.87; P = .0003).
Osimertinib Beats Chemo in Second-Line T790M-Mutant NSCLC
Osimertinib reduced the risk of disease progression by 70% compared with a chemotherapy doublet in patients with EGFR T790M-mutant non—small cell lung cancer who progressed after first-line targeted therapy, a benefit that was achieved with a dramatically lower rate of serious adverse events, according to phase III clinical trial results.
In the randomized AURA3 trial, patients who received osimertinib achieved a median progression-free survival of 10.1 months (95% CI, 8.3-12.3) compared with 4.4 months (95% CI, 4.2-5.6) for participants treated with a platinum agent plus pemetrexed (HR, 0.30; P <.001).
Ceritinib Improves PFS Over Platinum-Based Chemo in ALK+ NSCLC
Frontline treatment with ceritinib improved progression-free survival over standard chemotherapy in patients with ALK-rearranged non—small cell lung cancer, according to results from the phase III ASCEND-4 trial. Median PFS was 16.6 months (95% CI, 12.6-27.2) compared with 8.1 months (95% CI, 5.8-11.1) with chemotherapy (HR, 0.55; P <.001).
The ORR with ceritinib was higher at 72.5% compared with 26.7% in the chemotherapy group. The median duration of response (DOR) was 23.9 months versus 11.1 months, respectively. The relevance of this study was also questioned by those in attendance. The frontline standard of care is crizotinib, not chemo, making the comparator arm in this study obsolete.
FDA Grants Priority Review to Durvalumab in Bladder Cancer
The FDA has granted a priority review to a biologics license application for durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed on standard platinumâ€‘based chemotherapy. The BLA is based on data from the phase I/II Study 1108, in which durvalumab induced a response rate of 46% in patients with PD-L1—positive advanced bladder cancer. Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final approval decision by the second quarter of 2017.
FDA Approves Bevacizumab for Platinum-Sensitive Ovarian Cancer
The FDA has expanded the approval for bevacizumab in ovarian cancer to include patients with platinum-sensitive recurrent disease as part of a combination regimen with chemotherapy followed by continued use of the angiogenesis inhibitor. The approval is based on results from 2 randomized controlled phase III studies, GOG-0213 and OCEANS.
Both studies demonstrated a significant improvement in progression-free survival. GOG-0213 demonstrated that adding bevacizumab to chemotherapy led to a non-statistically significant median overall survival difference of 5 months compared with chemotherapy alone (42.6 months vs 37.3 months, respectively; HR, 0.84).
The OCEANS study, which enrolled 484 women, showed a median PFS improvement of 4 months for bevacizumab with chemotherapy versus placebo plus chemotherapy (12.4 months vs 8.4 months, respectively; HR, 0.46, 95% CI, 0.37-0.58; P <.0001).