CHICAGO (TheStreet) -- Four clinical trials involving the checkpoint inhibitors from Merck MRK and Bristol-Myers Squibb (BMY) are showing promising signs of efficacy in a wide range of solid tumors, according to results unveiled for the first time Friday at the start of the American Society of Clinical Oncology (ASCO) annual meeting.
The class of cancer immunotherapy drugs which target the protein PD-1 has already dramatically improved treatment options, including prolonged survival, for patients with skin cancer. Now, the same drugs are proving to be effective against advanced liver, head and neck, lung and colon cancers.
In some cases, doctors are able to look at the genetic signature of the tumors to determine in advance which patients may benefit most from treatment with checkpoint inhibitors.
The ASCO annual meeting doesn't usually get rolling until Saturday morning. This year is different. ASCO scheduled a media briefing Friday afternoon so researchers could discuss data on four studies involving checkpoint inhibitors. The highlights:
- Merck's Keytruda demonstrated a 62% tumor shrinkage in patients with advanced colon cancer containing a newly discovered genetic biomarker.
- The tumor response rate to Bristol's Opdivo in patients with advanced liver cancer was 19%. The overall survival rate at 12 months was 62%. While early, the results suggest Opdivo may have a role to play in the treatment of the disease where only a single targeted drug has proven effective.
- In a study of patients with head and neck cancer, Merck's Keytruda demonstrated a tumor response rate of 25%, or more than double the response typically seen with Eli Lilly's Erbitux.
- In the only randomized study discussed Friday enrolling patients with advanced, non-squamous, non-small cell lung cancer (the most common form of lung cancer) treatment with Bristol's Opdivo led to a 27% reduction in the risk of death compared to a placebo. Patients with tumors expressing high levels of the protein PD-1 lived even longer.
Roche's (RHHBY) Avastin is currently the most broadly used targeted cancer treatment, with approvals in six different solid tumors. Avastin kills tumors by shutting down their blood supply. Cancer immunotherapies work differently by stimulating the patient's own immune system to identify and kill cancer. More specifically, the checkpoint inhibitors work by blocking a protein used by cancer cells to hide from the immune system.
Pretty soon, based on data being presented at this year's ASCO meeting and on clinical trials still underway, the checkpoint inhibitor class of drugs is likely to match or exceed Avastin's number of approved cancer indications and take over as the new cornerstone of cancer therapy. Bristol and Merck are leading the way in cancer immunotherapy but Roche, AstraZeneca (AZN) and other large pharmaceutical companies are also developing competing checkpoint inhibitors.New biomarker for colon cancer
A phase II study identified a genetic marker -- mismatch repair (MMR) deficiency -- which predicts superior response to Merck's Keytruda, researchers said Friday. The study was conducted in patients with colon cancer but MMR deficiency is found in other solid tumors as well.
Tumors that are MMR deficient have many more genetic mutations compared to tumors containing MMR. The higher number of genetic mutations increases the probability that the immune system can recognize and destroy the tumor. For the same reason, researchers believed checkpoint inhibitors would be more effective in MMR-deficient cancers.
The thesis proved correct in this phase II study. The response rate to Keytruda was 62% in patients with MMR-deficient colon cancer while zero responses were observed in patients with MMR-containing colon cancer. Another group of patients with MMR-deficient gastrointestinal cancers (excluding colon) was also enrolled in the study, with a response rate of 60%.
MMR deficiency is found in approximately 15-20% of non-inherited colon cancers. Larger studies are being planned to confirm the finding that MMR deficiency is a predictor of stronger response to checkpoint inhibitors.
Merck is also moving ahead with a registrational study of Keytruda in patients with MMR-deficient colon cancer. Before discovering this new biomarker, colon cancer was not thought to be a promising candidate for checkpoint inhibitor therapy, says Dr. Roy Barnes, Merck senior vice president, global clinical development.
Bristol's Opdivo shrunk liver cancer in eight of 42 patients evaluable in a phase I study. The 19% objective response rate was especially encouraging because three-quarters of the patients enrolled in the study had liver cancer progressing despite previous treatments. Nearly 70% of the patients were treated previously with Amgen's (AMGN) Nexavar -- the only targeted drug approved currently for liver cancer.
Responses to Opdivo have surpassed 12 months in four patients, while 62% of the patients overall were still alive after 12 months. Seventeen percent of patients experienced serious adverse events, including elevated liver enzymes and rash.
"While we have to verify this early signal in larger studies, this is one of the first signs that immunotherapy with immune checkpoint inhibitors will have a role to play in the treatment of liver cancer," said Dr. Anthony El-Khoueiry of the University of Southern California Norris Comprehensive Cancer Center.
The response rate for Amgen's Nexavar in liver cancer is typically around 2% and the average overall survival is in the range of 10 to 11 months.
Liver cancer is diagnosed in approximately 36,000 people in the U.S. each year. The disease is even more prevalent in Asia, and is the leading cause of cancer death worldwide.
Head and neck cancer
Twenty-five percent of patients with advanced head and neck cancer had a complete or partial response to Merck's Keytruda, according to results from a mid-stage study.
"The efficacy we saw was remarkable -- pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy cetuximab," said Dr. Tanguy Seiwert of the University of Chicago. Pembrolizumab and cetuximab are the scientific names for Keytruda and Eli Lilly's (LLY) Erbitux.
Current standard treatment for newly diagnosed head and neck cancer involves chemotherapy with or without Erbitux. When Erbitux is used alone in the second line, the response rate is usually in the range of 10-13%.
The study enrolled 132 patients with recurrent head and neck cancer, of which 59% were treated previously with two or more lines of therapy. Ten percent of patients experienced serious side effects, including fatigue, rash and itching. More serious immune-related side effects such as inflammation of the lung or colon occurred in fewer patients.
Head and neck cancer is the sixth most common cancer in the U.S. and worldwide. Patients with recurrent or metastatic head and neck cancer have a median overall survival of 10-12 months.
Merck is conducting two, phase III studies evaluating Keytruda versus standard treatment in patients with recurrent or metastatic head and neck cancer.
Most common form of lung cancer
A randomized, phase III study showed that Bristol's Opdivo helped patients with non-squamous, non-small cell lung cancer live almost three months longer, on average, than similar patients treated with the chemotherapy docetaxel.
Overall, Opdivo reduced the risk of death by 27% compared to docetaxel -- marking this the first study in which a checkpoint inhibitor prolonged survival in patients with the most common form of lung cancer.
Opdivo is already approved in the U.S. for previously treated, squamous cell lung cancer. With these new study results, Bristol is talking with regulators in the U.S. and Europe about getting Opdivo approved for patients with previously treated non-squamous lung cancer, said Fouad Namouni, Bristol's vice president, head of Opdivo/Yervoy clinical development.
The study enrolled 582 patients and randomized them to treatment with Opdivo or docetaxel, used commonly today as a second-line treatment for non-squamous lung cancer.
Median overall survival in the Opdivo-treated patients was 12.2 months compared to 9.4 months for the docetaxel-treated patients. In a subgroup of patients with lung cancer expressing high levels of the protein PD-1, the median survival in the Opdivo patients exceeded 17 months compared to 9 months for docetaxel.
To put these Opdivo survival results for second-line lung cancer patients in perspective, consider that today's current standard of care for newly diagnosed lung cancer extends survival by about one year, said Bristol's Namouni.
Ten percent of Opdivo patients experienced serious side effects compared to half of patients treated with docetaxel. Due to serious side effects, 5% of Opdivo patients discontinued from the study compared to 15% in the docetaxel arm.