A triple-play against cancer
With the week still young, Roche, GlaxoSmithKline (GSK) and Bristol-Myers Squibb Co. (BMS) all have made significant splashes with regard to cancer news, with a promising antibody-drug conjugate (ADC), a pair of tantalizing metastatic melanoma drugs and an anti-PD-1 immunotherapy for non small-cell lung cancer (NSCLC), metastatic melanoma and renal cell carcinoma.
Roche, for its part, announced that the Phase III EMILIA study of trastuzumab emtansine (T-DM1) met its co-primary endpoint, which was the significant improvement in the time patients with HER2-positive metastatic breast cancer lived without their disease getting worse, otherwise known as progression-free survival. The study showed that the risk of disease worsening or death was reduced by 35 percent for people who received trastuzumab emtansine compared to those who received lapatinib plus Xeloda (capecitabine) chemotherapy. A trend was also shown for patients who received trastuzumab emtansine to live longer (overall survival, which was the other co-primary endpoint of the study) than those who received lapatinib plus Xeloda—but Roche stresses that the overall survival data are not yet mature.
The safety profile of trastuzumab emtansine was consistent with that seen in previous studies, Roche notes, with fewer patients who received trastuzumab emtansine experiencing Grade 3 or higher (severe) adverse events than those who received lapatinib plus Xeloda (40.8 percent compared to 57 percent).
"The encouraging efficacy, safety profile and quality-of-life results from the EMILIA study support our belief that trastuzumab emtansine may have an important role for patients with HER2-positive metastatic breast cancer," said Dr. Hal Barron, chief medical officer and head of global product development at Roche. "We are working with global regulatory authorities to submit these data as quickly as possible and hope that trastuzumab emtansine will soon be available to patients with this aggressive type of breast cancer."
With two anti-cancer agents to show, GSK released findings for its Phase III clinical study program evaluating single-agent therapy with the compounds dabrafenib and trametinib in patients with BRAF V600 mutation-positive metastatic melanoma.
Both the BREAK3 study of dabrafenib (a BRAF inhibitor) and the METRIC study of trametinib (a MEK inhibitor) demonstrated a statistically significant benefit in progression-free survival or PFS) compared to those receiving chemotherapy. Additionally, patients in the METRIC study who received trametinib seem to demonstrate better overall survival than those who received chemotherapy with dacarbazine; however, the overall survival data are not yet mature in the BREAK3 trial.
"The results from the clinical studies of dabrafenib and trametinib … represent important progress towards understanding how these investigational agents could benefit patients with advanced and metastatic melanoma. Importantly, trametinib is the first MEK inhibitor to demonstrate clinical benefit in a late phase melanoma trial." said Dr. Rafael Amado, head of oncology research and development for GSK. "We are planning regulatory submissions for dabrafenib and trametinib as single-agent therapies and have recently started a Phase III program to further investigate the effect of the combination in this disease."
Finally, BMS has earlier-stage but still promising data, announcing interim results from the expanded Phase I dose-ranging study of its investigational anti-PD-1 immunotherapy BMS-936558, which showed clinical activity in patients with previously-treated NSCLC, metastatic melanoma and renal cell carcinoma.
As BMS explains, anti-PD-1 is a fully-human antibody that targets the inhibitory receptor expressed on activated T-cells called PD-1, or programmed death-1. Objective response rates across dose cohorts, as measured by standard RECIST criteria, ranged from 6 percent to 32 percent in NSCLC, 19 percent to 41 percent in metastatic melanoma and 24 percent to 31 percent in renal cell carcinoma, with BMS reported that "most responses were durable."
"Immuno-oncology is a prioritized area of research and development at Bristol-Myers Squibb and we plan to initiate registrational studies for anti-PD-1 in NSCLC and RCC this year and late 2012, early 2013 for metastatic melanoma," said Brian Daniels, senior vice president of global development and medical affairs at BMS.