Bladder Cancer Drug Rejection Highlights Cancer News of the Week

Top news of the week in oncology, and cancer drug development.

ODAC Unanimously Rejects Apaziquone for Bladder Cancer

The FDA’s Oncologic Drugs Advisory Committee voted 14-0 against approving apaziquone for intravesical instillation immediately following transurethral resection in patients with non-muscle invasive bladder cancer. The panel considered a new drug application for apaziquone based on findings from 2 phase III trials (identified as 611 and 612), which both missed the primary endpoint of a statistically significant reduction in disease recurrence at 2 years with a single dose of apaziquone versus placebo.

In study 611, 38% (112/295) of patients with TaG1-2 disease in the apaziquone arm had disease recurrence compared with 44.6% (121/271) of patients in the placebo arm. In study 612, 40.4% (114/282) of patients with TaG1-2 disease in the apaziquone arm had disease recurrence compared with 46.6% (139/298) of patients in the placebo arm. The submission followed a pooled analysis of these two trials that seemed to show some benefit for the drug in certain settings.

An ongoing phase III trial designed through a special protocol assessment with the FDA is examining the impact of the timing of treatment, as well as the effect of administering a second dose of apaziquone. Spectrum will now await a final decision on apaziquone from the FDA, which is scheduled to be made on or before December 11, 2016, under the Prescription Drug User Fee Act. The FDA usually follows the recommendations of ODAC.

See more http://www.onclive.com/web-exclusives/fda-panel-votes-against-apaziquone-in-bladder-cancer

CHMP Adopts Positive Opinion for Ixazomib in Myeloma

The Committee for Medicinal Products for Human Use has recommended a conditional approval for ixazomib in combination with lenalidomide and dexamethasone as a treatment for patients with multiple myeloma who have received at least 1 prior therapy, based on finding from the phase III TOURMALINE-MM1 study. Findings from the trial demonstrated a 26% reduction in the risk of disease progression or death with the ixazomib triplet versus a doublet of lenalidomide and dexamethasone alone.

Median progression-free survival with the ixazomib triplet was 20.6 months compared with 14.7 months with the doublet (HR, 0.74; P = .01). Earlier this year, the CHMP issued a negative opinion for ixazomib's marketing authorization, due to a paucity of data to support a full authorization, the agency said. In June 2016, Takeda requested a re-examination of the application on the basis of a conditional approval, which led to the newly adopted positive opinion. Under this program, the company will be required to submit additional data from ongoing studies to support continued authorization.

See more http://www.onclive.com/web-exclusives/chmp-issues-positive-opinion-for-ixazomib-conditional-approval-in-myeloma

Palbociclib Nears Approval in Europe

The Committee for Medicinal Products for Human Use has recommended approval of palbociclib for patients with HR-positive, HER2-negative metastatic breast cancer, either in combination with an aromatase inhibitor in the frontline setting, or combined with fulvestrant after progression on endocrine therapy. The application for the CDK 4/6 inhibitor is based on findings from the PALOMA-1, PALOMA-2, and PALOMA-3 trials.

The positive opinion has been sent to the European Commission, which usually issues its final approval decision within 2 to 3 months of the CHMP recommendation. In PALOMA-1, palbociclib plus letrozole reduced the risk of disease progression by 51% compared with letrozole alone. The median progression-free survival with palbociclib was 20.2 versus 10.2 months for letrozole alone (HR, 0.49; P = .0004). In PALOMA-2, The median PFS by blinded independent central review was 30.5 months versus 19.3 months, respectively (HR, 0.65; P = .0005). In PALOMA-3, the median PFS was 9.5 months with the palbociclib plus fulvestrant versus 4.6 months in the placebo arm (HR, 0.46; P <.0001).

See more http://www.onclive.com/web-exclusives/chmp-issues-positive-opinion-for-palbociclib-in-hrher2-breast-cancer

Olaratumab Approval Approaching for Sarcoma

The Committee for Medicinal Products for Human Use has recommended approval of the PDGFRα antagonist olaratumab for use in combination with doxorubicin for patients with advanced soft tissue sarcoma who are not good candidates for radiotherapy or surgery. The positive opinion has been sent to the European Commission, which usually issues its final approval decision within 2 to 3 months of the CHMP recommendation.

In the United States, the FDA granted a priority review to olaratumab for use in combination with doxorubicin in this setting in May 2016. A decision is expected by November 4, 2016. Both the EU and US applications for olaratumab were based on data from the phase II JGDG trial, in which combining olaratumab with doxorubicin reduced the risk of death by 54% versus doxorubicin alone in patients with STS (HR, 0.46; P = .0003). The median overall survival in the intent-to-treat population (n = 129) was 11.8 months higher with the olaratumab combination versus doxorubicin alone.

See more http://www.onclive.com/web-exclusives/chmp-adopts-positive-opinion-for-olaratumab-in-soft-tissue-sarcoma

Two TKIs Approved for RCC in Europe

The European Commission has approved lenvatinib in combination with everolimus for patients with advanced renal cell carcinoma following 1 prior VEGF-targeted therapy. Additionally, the agency approved cabozantinib for the treatment of patients with advanced RCC after the failure of VEGF-targeted therapy. The approval for lenvatinib was based on findings from a phase II study, which showed a 60% reduction in the risk of progression or death with the combination versus single-agent everolimus.

Median progression-free survival with the combination was 14.6 months versus 5.5 months with everolimus (HR, 0.40; P = .0005). The median overall survival with lenvatinib plus everolimus was 25.5 months compared with 15.4 months with everolimus alone (HR, 0.59; 95% CI, 0.36-0.97).

See more http://www.onclive.com/web-exclusives/ec-approves-lenvatinibeverolimus-combo-for-rcc

The approval for cabozantinib was based on findings from the phase III METEOR trial, in which the most recent data showed that cabozantinib produced a 4.9-month median OS benefit versus everolimus. The risk of disease progression was reduced by 49% with cabozantinib over everolimus. Median OS was 21.4 months for patients receiving cabozantinib versus 16.5 months for those receiving everolimus (HR, 0.66; P = .0003). Both drugs are already approved in the United States.

See more http://www.onclive.com/web-exclusives/ec-approves-cabozantinib-for-renal-cell-carcinoma