By Ruchi Jhonsa, Ph.D.
Merck today announced the success of its pivotal Phase 3 KEYNOTE-355 trial investigating Keytruda’s role in combination with chemotherapy in patients with metastatic triple-negative breast cancer. Analyzed by an independent Data Monitoring Committee (DMC), the first line of treatment with Keytruda showed significant improvement in the progression free survival (PFS) combined with nab-paclitaxel, paclitaxel or gemcitabine mediated chemotherapy. DMC gave a green signal to the trial and recommended the trial shall continue without any changes to evaluate the other dual primary endpoint of overall survival. The findings of the trial will be shared with the medical community at an upcoming congress and the results will be discussed with the FDA and other regulatory authorities.
Triple Negative Breast Cancer (TNBC)
TNBC is an aggressive cancer that accounts for 10-15% of all breast cancers and is characterized by onset at a younger age, high recurrence rates, high mean tumor size, and high-grade tumors. It is named so because it is negative for all the three hormone receptors namely estrogen, progesterone and growth factor receptor 2, which are present in other types of breast cancers. Due to the absence of hormone receptors in TNBC, it is difficult to treat cancer with conventional hormonal or drug therapy.
One Drug to Treat Them All
Keytruda is an immunotherapy-based drug that treats cancers by boosting the natural immune response of the body. It is known that certain cancers can hide from the natural immune response by activating the PD-1 pathway. Our own body cells naturally use this mechanism to evade attack by immune cells. By using this pathway, cancer cells prevent lymphocytes from recognizing them as a foreign entity and shuts down their response against them.
Keytruda works by inhibiting this pathway. It is a humanized monoclonal antibody against PD-1 that releases the inhibition on T lymphocyte and makes it active against cancer cells. However, there is a huge side effect associated with the drug. Since the drug inhibits the PD-1 pathway on lymphocytes, it also makes lymphocytes active against self-organs, thereby generating an autoimmunity response. Keytruda is currently being investigated in 1000 clinical trials and is already approved for the treatment of melanoma, non-small cell lung cancer, head and neck squamous cell cancer, and several other cancer types that express PD-L1.
The keynote-355 is a randomized, Phase 3 trial that was conducted in two parts. The first part was an open-label study where safety and tolerability of Keytruda plus three chemotherapy drugs were compared to placebo with a similar combination of three chemotherapy drugs in 30 patients. Part 2 of the study was double-blinded, with dual primary endpoints of overall survival and progression free survival in all participants. Secondary endpoints of the trial include objective response rate, duration of response, disease control rate and safety. Part 2 of KEYNOTE-355 enrolled 847 patients who were randomized to receive Keytruda on day 1 of each 21day cycle along with nab-paclitaxel or paclitaxel on day 1, 8 and 15 of each 28-day cycle or gemcitabine/carboplatin on day 1 and 8 of each 28-day cycle.
This is yet another feather in Merck’s crown. Looking at the results, Roger M. Perlmutter, President, Merck Research Laboratories said, “It is very encouraging that Keytruda in combination with chemotherapy has now demonstrated positive results as both a first-line treatment in the metastatic setting with this trial, and as neoadjuvant therapy in the KEYNOTE-522 trial.”
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