Two phase 3 studies found that women with metastatic breast cancer survived longer when they received combination therapy with standard treatment and an additional drug, according to the results of recent studies presented at the annual meeting of the European Society for Medical Oncology (ESMO). The MONALEESA-2 study found that adding Kisqali (ribocliclib), a category of drugs known as CDK4 / 6 inhibitors, to hormone treatment increased survival of women with hormone receptor positive (HR positive), HER2 negative advanced Breast cancer prolonged. Similarly, the results of the KEYNOTE-355 study showed increased survival in women whose metastatic triple negative breast cancer (TNBC) expressed a biomarker known as PD-L1.
MONALEESA-2: Kisqali Plus Standard Hormone Therapy Extends Survival in Metastatic HR-Positive / HER2-Negative Breast Cancer by One Year
What’s new Postmenopausal women with HR-positive, HER2-negative advanced breast cancer who received Kisqali in addition to standard Femara hormone therapy (letrozole) survived one year longer than women who received Femara alone. CDK4 / 6 inhibitors target proteins known as cyclin-dependent kinases 4 and 6 and disrupt the division and reproduction of cancer cells.
Study details In this Phase 3 clinical trial, known as MONALEESA-2, the researchers randomly assigned 668 women to receive Femara plus either Kisqali or a placebo. The process took place in 29 countries in America, Europe and Asia. The primary results of MONALEESA-2 appeared in the New England Journal of Medicine in November 2016 when researchers reported that cancer did not progression for a median of 25.3 months in women who received Kisqali. However, the women in the Femara-only group had a median disease progression after 16 months. In the current study, which was presented at ESMO, the researchers rated overall survival at a predetermined point in time: the death of 400 study participants. Follow-up data showed that women who received Kisqali survived a median of 63.9 months, compared with 51.4 months for Femara alone. MONALEESA-2 researchers are continuing to investigate whether some patients responded better to the combined treatment than others.
Why it matters MONALEESA-2 is the first study to report a statistically significant and clinically meaningful overall survival benefit for these patients. “In my 45 years as an oncologist, a [progression-free survival] the benefit has been shown many times [but] We have rarely seen improvements in overall survival, ”said study author Gabriel N. Hortobagyi, MD, of the MD Anderson Cancer Center at the University of Texas at Houston. “It is difficult to show a statistically significant increase in survival for first-line therapy in this type of breast cancer” [because] In the course of their illness, patients receive 4 to 15 different types of treatment that weaken the effect of the first therapy. “
KEYNOTE-355: Keytruda Plus Chemotherapy Increases Survival in Women with PD-L1 Positive Metastatic TNBC
What’s new In the Phase 3 study known as KEYNOTE-355, researchers looked at Keytruda, a type of immunotherapy drug known as an immune checkpoint inhibitor, as well as a standard chemotherapy versus chemotherapy alone in women with PD-L1 positive metastatic TNBC, their tumors also positive for PD. were -L1, a biomarker suggesting that the tumor is responsive to checkpoint inhibitors. Women survived seven months longer than they received Keytruda, according to study results presented at ESMO.
Study details KEYNOTE-355 is a double-blind study in which researchers 847 women with recurrent, unresectable or metastatic TNBC were randomly assigned a standard chemotherapy chosen by their doctor plus either Keytruda or a placebo. In each treatment group, about 4 out of 10 women had high levels of PD-L1 expression in their tumor. Women with high PD-L1 expression in their tumor, according to the final KEYNOTE-355 results, had the largest survival gains with Keytruda with a median survival of 23 months compared to a median survival of 16.1 months for women who received chemotherapy only received. After 18 months of follow-up, 58.3 percent of women in the Keytruda group with high PD-L1 expression were still alive, while only 44.7 percent of women who received chemotherapy only. After two years of follow-up, 48.2 percent of the women in the Keytruda group were still alive, compared with only 34 percent of the women in the chemo-only group. The total median follow-up was 44 months in both groups. “Only women whose cancer expresses higher PD-L1 levels benefit significantly from adding pembrolizumab to chemotherapy,” said study author Hope S. Rugo, MD, of the University of California at San Francisco.
Why it matters Triple-negative breast cancer is aggressive and tends to occur more often in people younger than 40 years old, black Americans, or who have a BRCA1 mutation. On November 13, 2020, the Food and Drug Administration granted Keytruda accelerated approval in combination with chemotherapy for the treatment of patients with locally recurrent, inoperable, or metastatic TNBC whose tumors express high PD-L1 levels. This accelerated approval was based on the progression-free survival data of KEYNOTE-355. Now that the final overall survival data for the study are in, oncologists should be even more likely to use this treatment option for patients with PD-L1 positive TNBC, said Dr. Rugo.
Gonzalo Gomes-Abuin, MD, of Hospital Alemán in Buenos Aires, Argentina, who is not involved in KEYNOTE-355, agreed. “This very important, very well-designed study shows that pembrolizumab plus chemotherapy is a transformative treatment and should become the new standard of care for a subset of patients with PD-L1 positive metastatic TNBC,” he said.
DESTINY-Lung01: Promising results for Enhertu in HER2-mutated metastatic lung cancer
What’s new In an international phase 2 study, researchers observed good results in patients with metastatic lung cancer that carries a HER2 mutation who received Enhertu (trastuzumab deruxtecan), a HER2-antibody-drug conjugate that is also used to treat metastatic HER2 -positive breast and stomach cancer is used. (Antibody-drug conjugates are therapies that combine a targeted antibody with a cancer-killing drug.)
Study details The researchers treated 91 patients with HER2-mutated metastatic lung cancer with Enhertu and then watched how they responded to the drug at two doses. Two thirds of the participants were women and almost 60 percent had never smoked.
Fifty participants, or 55 percent, had a measurable response to Enhertu. One patient had a complete response, meaning the cancer went away, while 49 patients saw their disease improve. The median duration of response was 9.3 months and the median follow-up time was 13.1 months.
Almost half of the participants developed a moderate to severe side effect related to the Enhertu. These side effects caused about a quarter of the participants to discontinue the study. By mid-September, 15 patients were still taking the drug.
“DESTINY-Lung01 provides strong evidence of a positive benefit-risk balance for Enhertu and supports its establishment as a potential new standard of care,” said Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
As a phase 2 study, DESTINY-Lung01 cannot make any comparisons between competing treatments. Phase 2 studies are used to test the safety and effectiveness of drugs. Researchers’ preferred dose of Enhertu is moving into a larger global phase 2 study, DESTINY-Lung02, which is now enrolling patients.
Why it matters About 3 percent of patients with non-small cell lung cancer (NSCLC) have a HER2 mutation. These patients, who are usually women who have never smoked, have a poor prognosis and a higher risk of developing brain metastases. There are currently no approved HER2-directed therapies for patients with NSCLC, and oncologists do not routinely test patients with lung cancer for a HER2 mutation. You will typically receive standard chemotherapy, immunotherapy, or both. If the disease recurs, oncologists see improvement in no more than a quarter of patients, so there is an urgent need for new treatments for these patients.