Drug Approvals and Priority Reviews Highlight Cancer Treatment News
Latest developments in oncology drug research.
Atezolizumab/Nab-Paclitaxel Highly Effective in Breast Cancer
Upfront treatment with the PD-L1 inhibitor atezolizumab plus nab-paclitaxel showed a confirmed objective response rate of 66.7% in patients with metastatic triple-negative breast cancer. In the phase Ib study, atezolizumab plus nab-paclitaxel was explored across several lines of treatment regardless of PD-L1 status for patients with metastatic TNBC. In the second-line setting, the confirmed ORR was 25% and in the third-line and beyond the ORR was 28.6%. Across the full trial, the ORR was 41.7%.
When considering unconfirmed responses, the ORR was 70.8%, which included a complete response rate of 4.2%. In patients with PD-L1—positive TNBC, the ORR was 77.8% and the stable disease rate was 22.2%. In the unknown biomarker arm, the ORR was 75%, which included 1 complete response and 2 patients with progressive disease. In the PD-L1–negative group, the ORR was 57.1% and the stable disease rate was 42.9%.
Pembrolizumab Effective in ER-Positive Breast Cancer
The PD-1 inhibitor pembrolizumab had an overall response rate of 12% in PD-L1—positive patients with ER+/HER2- advanced breast cancer. At a median follow-up of 7.3 months, the ORR was comprised of all partial responses and no complete responses.
The median time to response was 8 weeks and the median duration of response has not yet been reached, ranging from 8.7 to >44 weeks. Four patients (16%) had stable disease, with a median duration of 16 weeks. The clinical benefit rate, defined as partial response plus stable disease for ≥24 weeks, was 20% (n = 5). Fifteen patients (60%) had progressive disease.
Among 22 patients who had at least 1 scan following baseline, ORR was 14% and the clinical benefit rate was 23%. The results mark the second early-stage trial to show antitumor activity with pembrolizumab in breast cancer. In previously reported data from the phase Ib KEYNOTE-012 trial, pembrolizumab demonstrated an ORR of 18.5% in patients with PD-L1­—positive triple-negative breast cancer.
Neratinib 3-Year ExteNET Data Similar to Primary Analysis
Neratinib continued to show similar rates of disease-free survival for patients with HER2-positive early-stage breast cancer, according to a 3-year exploratory analysis of the ExteNET trial. The updated 3-year invasive DFS rate was 92% with neratinib versus 89.9% for placebo (HR, 0.74; 95% CI, 0.56-0.96; P = .023). In those specifically with centrally confirmed HER2-positive/HR-positive breast cancer, the 3-year DFS rate was 94.4% versus 88%, for neratinib and placebo, respectively (HR, 0.43; 95% CI, 0.26-0.70; P <.001).
In the HR-negative group, there was no improvement seen between the neratinib group and the placebo arm, suggesting a distinct population that benefits from the TKI. In the HR-negative group, invasive DFS rate with neratinib was 88.1% versus 89.5% with placebo (HR, 0.98; 95% CI, 0.67-1.45; P = .938). Quality of life scores by FACT-B were distinctly worse during the first 30 days in the neratinib arm, related to diarrhea; however, after 30 days, the two groups reported similar scores.
Buparlisib Modestly Effective in Breast Cancer
Treatment with the PI3K inhibitor buparlisib plus fulvestrant showed a 1.9-month extension in progression-free survival compared with fulvestrant alone in women with endocrine-resistant HR-positive/HER2-negative advanced breast cancer, according to data from the phase III BELLE-2 trial. Median PFS with buparlisib plus fulvestrant was 6.9 versus 5.0 months for placebo plus fulvestrant (HR, 0.78; 95% CI, 0.67-0.89; P <.001).
In a group of patients with PIK3CA mutations identified by circulating tumor DNA, the benefits seen with buparlisib were more substantial. In this group, median PFS with the PI3K inhibitor was 7.0 versus 3.2 months with placebo (HR, 0.56; P <.001). While the future is unclear for buparlisib, the phase III SOLAR-1 study is currently assessing the alpha-specific PI3K inhibitor alpelisib (BYL719) in combination with fulvestrant as a treatment for postmenopausal women with endocrine-resistant advanced breast cancer. PIK3CA mutation status by ctDNA will be assessed as a secondary endpoint.
Avelumab Effective in PD-L1-Positive Breast Cancer
Treatment with the PD-L1 inhibitor avelumab demonstrated promising overall response rates for patients with PD-L1—positive metastatic breast cancer, particularly for those with triple-negative disease, according to findings from a phase Ib study. After a median follow-up of 10 months, the ORR in patients with PD-L1-expressing metastatic breast cancer was 33.3%.
In patients with PD-L1-positive triple-negative breast cancer, the ORR was 44.4% with avelumab. Across the full study population, which included PD-L1-negative patients, the ORR was 4.8% (95% CI, 2.1-9.2). In the full population of the study, the ORR included 1 CR and 7 PRs. An additional 23.2% of patients experienced stable disease with avelumab, for a disease control rate of 28%. Of those who responded, 5 had TNBC (8.6%), 4 of which were PD-L1-positive.
Responses were also observed in patients with HER2-negative/HR-positive breast cancer (2.8%) and for those with HER2-positive disease (3.8%).
Adding Denosumab Improves DFS in Breast Cancer
A follow-up analysis of the benefits of adding denosumab to an aromatase inhibitor has found that the agent not only helps to prevent fractures, it reduces the risk of recurrence and death in postmenopausal women with HR-positive breast cancer. In this phase III trial, a 19% relative survival improvement was seen among women who had denosumab added to their AI therapy, suggesting that the agent should be recommended in this setting, regardless of the patient’s bone health status.
The absolute benefit was about 1% after 3 years, 2% after 5 years, and 3% after 7 years of follow up. Additionally, benefits may be greater for those who start their treatment earlier (HR, 0.61), patients with larger tumors (HR, 0.66), those with ductal invasive histology (HR, 0.79), and patients whose tumors are HR-positive (HR, 0.75).
FDA Approves Alectinib for ALK-Positive NSCLC
The FDA granted an accelerated approval to alectinib as a treatment for patients with metastatic ALK-positive non—small cell lung cancer following progression on crizotinib, based on objective response rates in two phase II clinical trials. In the first study, labeled NP28761, the ORR with alectinib was 38% by independent review and 46% by investigator assessment.
The duration of response was 7.5 months. For the second trial, known as NP28673, the ORR was 44% by independent review, 48% by investigator assessment, and the duration of response was 11.2 months. In the NP28761 trial, the median progression-free survival, although not yet mature, was 6.3 months. In NP28673, the median PFS was 8.9 months.
A pooled analysis of the two studies was conducted for 51 patients with CNS metastases. Across the studies, 69% of patients had received prior brain radiation, with nearly half of patients completing radiation (49%) at least 6 months prior to receiving alectinib.
FDA Approves Cooling Cap to Prevent Hair Loss
The Dignitana DigniCap Cooling System, a computer-controlled device aimed to reduce the severity and frequency of hair loss in patients who receive neoadjuvant or adjuvant chemotherapy for breast cancer, has been cleared by the FDA as the first cooling cap for use in the United States. The clearance is based on a multicenter, FDA-approved clinical trial examining the effects of the scalp hypothermia system in 122 women with stage I/II breast cancer who were undergoing alopecia-inducing chemotherapy.
Results of the open-label, nonrandomized study showed that more than 66% of the women who used the device lost less than 50% of their hair. The trial’s primary endpoint was a self-assessment of hair loss. Patients photographed their hair 3 to 6 weeks after their last chemotherapy treatment, and provided a satisfaction score, ranked 0 to 100 with 100 being “completely satisfied.”
The mean satisfaction score with the decision to use scalp cooling was 87.5, the mean hair quantity score was 70.9, and a mean score of 69.1 was reported for hair quality.
Priority Review Granted to Palbociclib Plus Fulvestrant
The FDA granted a priority review to a supplemental new drug application for palbociclib for use in combination with fulvestrant in pretreated patients with HR-positive, HER2-negative metastatic breast cancer, according to Pfizer, the manufacturer of the CDK 4/6 inhibitor. The FDA is scheduled to make its approval decision by April 2016.
The priority review is based on findings from the phase III PALOMA-3 trial, in which adding palbociclib to standard fulvestrant more than doubled progression-free survival in pretreated patients with HR-positive, HER2-negative breast cancer. Palbociclib delayed disease progression by over 5 months.
Median PFS was 9.2 months with the palbociclib combination versus 3.8 months in the placebo arm (HR, 0.422; 95% CI 0.318-0.560; P <.000001). The PFS benefit was observed regardless of menopause status and remained consistent across all prespecified patient subgroups. OS data are not yet mature.
FDA Approves Bendamustine Hydrochloride for CLL, NHL
The FDA has approved a rapid infusion formulation of bendamustine hydrochloride under the trade name Bendeka for the treatment of patients with chronic lymphocytic leukemia or indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. The overall response rate with Bendeka in CLL was 59%, with a complete response rate of 8%.
For those in the chlorambucil arm, the ORR was 26%, with a CR rate of <1%. The median progression-free survival with Bendeka was 18 months versus 6 months with chlorambucil (HR, 0.27; 95% CI, 0.17-0.43; P <.0001). In the NHL group, the ORR with Bendeka was 74%, with a CR rate of 13%. The unconfirmed CR rate was 4%. The duration of response was 9.2 months (95% CI, 7.1-10.8).
Priority Review to Crizotinib for ROS1 NSCLC
The FDA has granted a priority review to crizotinib as a treatment for patients with ROS1-positive metastatic non—small cell lung cancer, based on the demonstration of substantial efficacy in a phase I study. A final decision for crizotinib is expected from the FDA by April 2016.
In data from study, treatment with crizotinib elicited an overall response rate of 72% in patients with ROS1-rearranged NSCLC. There were 3 complete responses (6%) and 33 partial responses (66%). An additional 9 patients (18%) had stable disease as their best response for an overall disease control rate of 90%. The median progression-free survival with crizotinib was 19.2 months. At a median follow-up for overall survival of 16.4 months, the 12-month OS rate was 85%.
The median had not been reached. Many treatment guidelines have already included crizotinib as an option for ROS1-mutant NSCLC.
FDA Approves Uridine Triacetate for Chemo Overdose
The FDA has approved uridine triacetate for the emergency treatment of adult and pediatric patients who had severe or life-threatening toxicities within 4 days of treatment following an overdose of 5-fluorouracil or capecitabine. FDA’s decision was based on two, open-label clinical studies that measured the 30-day survival rate of adult and pediatric patients who had either overdosed on treatment or were experiencing early-onset toxicities.
Of those who overdosed, 97% treated with uridine triacetate were still alive after 30 days. Of those treated for toxicities, 89% were alive at 30 days. The approval marks the first emergency antidote for specific chemotherapies. Both trials showed that 33% of patients resumed chemotherapy within 30 days of being treated with uridine triacetate.