[Ben Fidler co-authored this report.] The European Society for Medical Oncology is wrapping up its annual conference today, replete with clinical data from cancer’s front lines. We’ve sorted the headlines into a few big categories: immunotherapy combinations, breast cancer, lung cancer, the growing class of drugs called PARP inhibitors, and new drugs that treat tumors based on genetic signature.
Patients with two different types of breast cancer got promising news at ESMO from studies exploring relatively new methods of treatment.
Drugs that boost a patient’s immune system to fight back against cancer have been approved to fight several types of cancer and have even become a first-line option against some advanced lung and kidney cancers. But experimental results unveiled over the weekend are the first in immunotherapy to show a survival benefit in breast cancer, which causes the second-most cancer deaths among U.S. women.
The results were in metastatic triple negative breast cancer (TNBC), a particularly aggressive form of the disease that cannot be treated with well-known drugs like trastuzumab (Herceptin) or hormone therapy. It represents about 15 to 20 percent of breast cancer cases, according to the Susan G. Komen advocacy group.
The Phase 3, 902-patient study, IMPassion130, showed patients taking Roche’s atezolizumab (Tecentriq) and Abraxane, a version of the chemotherapy paclitaxel sold by Celgene (NASDAQ: CELG), lived longer than patients on Abraxane alone. The difference was statistically significant in patients whose tumors carried the protein PD-L1, which atezolizumab targets. PD-L1-positive patients on atezolizumab-chemotherapy survived a median of 25 months following treatment, compared with 15.5 months for the chemo-only group.
“There are limited treatment options for TNBC and we think the combination could become the new standard of care for PD-L1 positive patients,” wrote Jeffries analyst Ian Hilliker in a note to investors.
Among all patients, regardless of PD-L1 status, median survival for the atezolizumab-chemo group was 21.3 months versus 17.6 months for chemotherapy alone, but it was not statistically significant. Investigators said it was likely because the results were interim; median follow-up was just short of 13 months. Another goal of the study was to measure progression-free survival, or the length of time before a patient’s tumor starts to grow again. Again, the results were better for PD-L1-positive patients, who constituted 41 percent of the study, than for the entire group.
Merck is following behind with pembrolizumab (Keytruda), which is being studied (Keynote-355) in metastatic triple negative breast cancer in combination with different chemotherapy combinations. Keynote-355 is due to reveal data at the end of 2019, though strong results could push an earlier disclosure, as happened last week with pembrolizumab in kidney cancer.
The second study to show good results from a new approach was targeting a different breast cancer: hormone-receptor (HR) positive, but HER2 negative, which means the tumor growth is fueled by hormones. The investigators gave patients alpelisib, a drug known as a PI3K inhibitor. Unlike other PI3K drugs, alpelisib only blocks one of the four main kinds of PI3K mutation, which could make for fewer side effects and let patients stay on alpelisib longer than other anti-PI3K drugs.
The “alpha” mutation that alpelisib targets is present in about 40 percent of HR-positive breast cancers, and 341 of the 572 women in the SOLAR-1 trial had the mutation. Patients taking alpelisib plus the chemotherapy fulvestrant saw their tumors held in check for a median of 11 months. Those taking fulvestrant only had 5.7 months. They were followed for a median of 20 months.
The follow-up time was not long enough to determine a survival benefit.
It remains to be seen how alpelisib, which is owned by Novartis (NYSE: NVS), might fit into the treatment landscape. A different type of drug blocking enzymes CDK4 and CDK6, which help tumor cells divide and grow, has become the standard of care for HR-positive breast cancer. Three drugs in this class have been approved, and an ESMO summary of the SOLAR-1 results cautioned that few patients in the study had been pretreated with CDK4/6 inhibitors.
Lung cancer is the biggest killer of all cancers in the U.S., with more than 150,000 estimated deaths this year.
Multiple immunotherapies are now approved for lung cancer, including a chemotherapy-immunotherapy combination from Merck that could become the new standard for non-small cell lung cancer, the most common form of the disease. That leadership position has come at the expense of Bristol-Myers Squibb, which has suffered a few clinical setbacks and disclosed another one as ESMO got underway on Friday. The FDA has delayed review of an immunotherapy combination, nivolumab (Opdivo) and ipilimumab (Yervoy), that Bristol wants to use to treat a subset of newly diagnosed lung cancer patients. Bristol’s shares sank 6.3 percent on Monday.
ESMO didn’t provide any landscape-shifting updates in lung cancer, but one tidbit emerged from Roche, which has been testing a number of combinations in a bid to grab slices of the market from Merck. Roche detailed the results of its IMpower130 study, which tested atezolizumab with two chemotherapies, carboplatin and Abraxane. Patients on atezolizumab-chemotherapy lived a median of 18.6 months, compared to 13.9 months for those on chemo alone. Here’s more on that study and Roche’s strategy from Fierce Pharma.
It’s well documented that single-agent immunotherapies can work wonders, but only in limited numbers of patients. The next frontier: combinations that hit tumors from two or more angles. But companies have been burned by moving too quickly.
—Merck shed a little light on a target called STING, or stimulator of interferon genes, which helps trigger immune response against invaders or tumors. (The idea is to boost STING, not block it.) A Merck STING drug on its own showed no effect in a range of tumors but fared a bit better when combined with pembrolizumab.
No word yet about a rival STING-PD-1 combination from Novartis and Aduro Biotech (NASDAQ: ADRO), also in Phase 1.
—Merck fared better doubling up pembrolizumab and chemo in first-line head-and-neck cancer, but … Next Page »