Puma Biotech Gets A Leg Up As Genentech Suffers Blow Over Breast Cancer Combo Therapy

– Phase III study confirms benefit of the Perjeta-based regimen over the current standard of care –

– The study was positive in the overall population, with greatest risk reduction in patients with node-positive or hormone receptor-negative disease –

– Data will be submitted to global health authorities –

CHICAGO--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), the Breast International Group (BIG), Breast European Adjuvant Study Team (BrEAST) and Frontier Science Foundation (FS) today announced the Phase III APHINITY study showed adjuvant (after surgery) treatment with the combination of Perjeta^® (pertuzumab), Herceptin^® (trastuzumab) and chemotherapy (the Perjeta-based regimen) significantly reduced the risk of breast cancer recurrence or death (invasive disease-free survival; iDFS) by 19 percent in people with HER2-positive early breast cancer (EBC) compared to Herceptin and chemotherapy alone (HR=0.81; 95% CI 0.66-1.00, p=0.045). At three years, 94.1 percent of people treated with the Perjeta-based regimen did not have their breast cancer return compared to 93.2 percent treated with Herceptin and chemotherapy. The safety profile of the Perjeta-based regimen was consistent with that seen in previous studies, with a low incidence of cardiac events and no new safety signals.

“The goal of adjuvant treatment is to help each person with cancer have the best chance of a cure, and we come closer to this goal with each advance”

Based on data available at the time of the primary analysis, an estimate of iDFS at four years showed that 92.3 percent of people treated with the Perjeta-based regimen did not have their breast cancer return compared to 90.6 percent treated with Herceptin and chemotherapy, suggesting that further analyses with longer follow-up will be important to provide additional insights on these treatments.

“The goal of adjuvant treatment is to help each person with cancer have the best chance of a cure, and we come closer to this goal with each advance,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “In the APHINITY study, the Perjeta-based regimen improved upon the high bar set by Herceptin in people with HER2-positive early breast cancer. We look forward to working with global health authorities to bring this treatment option to patients.”

Gunter von Minckwitz, M.D., study coordinator from the BIG and academic study partners, President of the German Breast Group, added, “APHINITY provides yet another example of the importance of industry-academic collaborations and their value in advancing cancer care for people affected by this challenging disease. The median follow-up at the primary analysis was 45.4 months, and these early data are very encouraging. As we continue to follow patients up to 10 years, we hope that future analyses will provide additional insights on the role of a pertuzumab-based regimen in HER2-positive early breast cancer.”

At the time of the primary analysis, with median follow-up of 45.4 months, the reduction in risk of invasive breast cancer recurrence with the Perjeta-based regimen was greatest in people with lymph node-positive (HR=0.77; 95% CI 0.62-0.96, p=0.019) or hormone receptor-negative disease (HR=0.76; 95% CI 0.56-1.04, p=0.085). At three years, among people with node-positive disease, 92.0 percent of people treated with the Perjeta-based regimen did not have their breast cancer return compared to 90.2 percent treated with Herceptin and chemotherapy, and iDFS rates in the hormone receptor-negative disease subgroup were 92.8 percent in the Perjeta-based arm and 91.2 percent in the Herceptin and chemotherapy arm. The number of events in both treatment arms was low in people with node-negative disease, where no benefit with the Perjeta-based regimen was detected at this time.

HER2-positive breast cancer is an aggressive form of the disease that affects approximately one in five people with breast cancer. Despite advancements in the treatment of HER2-positive EBC, one in four people treated with Herceptin and chemotherapy will eventually see their cancer return in the long-term. Treating breast cancer early, before it has spread, may help prevent the disease from returning and potentially reaching an incurable stage. Adjuvant therapy is given after surgery and is aimed at killing any remaining cancer cells to help reduce the risk of the cancer returning.

Full results of the primary analysis will be presented in an oral session today at the 53^rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago by Gunter von Minckwitz, M.D., study coordinator from the BIG and academic study partners (Abstract #LBA500), and will be featured in ASCO’s official press program. Results from the APHINITY trial will also be published today in the New England Journal of Medicine.

About APHINITY

APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, Phase III, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin and chemotherapy as adjuvant therapy in 4,805 people with operable HER2-positive EBC.

People enrolled in the study underwent surgery and were randomized to one of two arms (1:1) to receive either:

• Six to eight cycles of chemotherapy (anthracycline or non-anthracycline-containing regimen) with Perjeta and Herceptin, followed by Perjeta and Herceptin every three weeks for a total of one year (52 weeks) of treatment.
• Six to eight cycles of chemotherapy (anthracycline or non-anthracycline-containing regimen) with placebo and Herceptin, followed by placebo and Herceptin every three weeks for a total of one year (52 weeks) of treatment.

Radiotherapy and/or endocrine therapy could be initiated at the end of adjuvant chemotherapy. For people with hormone receptor-positive disease enrolled in the APHINITY trial, it was recommended that endocrine therapy be administered for at least five years after completing adjuvant chemotherapy. The APHINITY study allowed for a range of standard chemotherapy regimens to be used and participants with both node-positive and node-negative disease were eligible for enrollment. The primary efficacy endpoint of the APHINITY study is iDFS, which in this study is defined as the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival and health-related quality of life.

Median follow-up for ITT population 45.4 months
				Perjeta + Herceptin + chemotherapy n=2,400				Placebo + Herceptin + chemotherapy n=2,404
Invasive disease-free survival (iDFS) at 3 years
Intent-to-treat population (ITT) n=4,804				94.1% 171 events				93.2% 210 events
				HR=0.81; 95% CI 0.66-1.00, p=0.045
Node-positive subgroup n=3,005				92.0% 139 events				90.2% 181 events
				HR=0.77; 95% CI 0.62-0.96, p=0.019
Node-negative subgroup n=1,799				97.5% 32 events				98.4% 29 events
				HR=1.13; 95% CI 0.68-1.86, p=0.644
Hormone receptor-positive subgroup n=3,082				94.8% 100 events				94.4% 119 events
				HR=0.86; 95% CI 0.66-1.13, p=0.277
Hormone receptor-negative subgroup n=1,722				92.8% 71 events				91.2% 91 events
				HR=0.76; 95% CI 0.56-1.04, p=0.085
Estimate of invasive disease-free survival (iDFS) at 4 years*
Intent-to-treat population n=4,804				92.3%				90.6%
Node-positive subgroup n=3,005				89.9%				86.7%
Node-negative subgroup n=1,799				96.2%				96.7%
Hormone receptor-positive subgroup n=3,082				93.0%				91.6%
Hormone receptor-negative subgroup n=1,722				91.0%				88.7%
Safety
Grade 3 or higher adverse event (AE)				64.2%				57.3%
Fatal AE				0.8%				0.8%
Primary cardiac event**				0.7%				0.3%
				Difference 0.4%; 95% CI 0.0-0.8%
Most common (=5%) severe (Grade 3 or higher) AEs
Neutropenia Decrease in a certain type of white blood cell				16.3%				15.7%
Febrile neutropenia Fever associated with decrease in a certain type of white blood cell				12.1%				11.1%
Diarrhea				9.8%				3.7%
Diarrhea Onset after chemotherapy, during targeted therapy				0.5%				0.2%
Neutrophil count decreased Decrease in a certain type of white blood cell				9.6%				9.6%
Anemia Decrease in red blood cells or hemoglobin				6.9%				4.7%

* iDFS at four years was calculated based on data available at the time of primary analysis with median follow-up of 45.4 months

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