Cancer has evolved to protect itself from our inherent immune responses, and some types of cancer cells have developed their own strategies to evade or withstand treatment. These pro-cancer shields that tumors create to protect themselves make finding optimal cancer treatment regimens challenging. To combat these challenges, a significant amount of cancer research and drug/treatment development centers around combination therapeutic approaches, which target multiple pathways to exert the best result.
One type of combination treatment are adjuvant therapies. These treatments are given after primary treatment and provide a kind of backup plan to the first treatment approach. They can prevent the cancer from coming back or getting worse. For example, adjuvant chemotherapy following radiation or surgery has shown success in some diseases, includingbreast, pancreatic, and lung cancers.
A recent clinical trial investigated the efficacy of pelvic radiotherapy followed by adjuvant chemotherapy in women with endometrial cancer. The results of a clinical trial, recently published in The Lancet Oncology, show a long-term survival benefit of the combination approach.
The clinical trial, known as PORTEC-3 (NCT00411138), was a multi-institutional effort that included 660 women with high-risk endometrial cancer. Participants received treatment from over 100 different cancer centers across seven countries. Half of the participants received pelvic radiotherapy while the other half received radiotherapy combined with a chemotherapy regimen (chemoradiation). The patients in the chemoradiation group received two cycles of cisplatin, followed by four cycles of carboplatin and paclitaxel.
After treatment, the researchers followed the participants for an average of 10.1 years, proving strong data to support the long-term benefits of these treatment regimens. The analysis revealed over 7% better odds of 10-year survival for women receiving adjuvant chemotherapy compared to those receiving radiation alone (74.4% versus 67.3%). Further, the study also observed a benefit to 10-year recurrence-free survival, a measure of the likelihood of surviving 10 years past treatment without a cancer recurrence. Women receiving chemoradiation also exhibited better 10-year recurrence-free survival than those receiving radiotherapy alone (72.8% versus 67.4%).
The researchers also evaluated the molecular makeup of the tumors from some of the women in each treatment group, which suggests a role for p53, a tumor suppressor gene, in the mechanism driving the benefits of adjuvant chemotherapy in endometrial cancer patients. The molecular analysis showed that women whose tumors expressed a mutation in p53 experienced an even larger 10-year survival benefit with chemoradiation (52.7% for adjuvant chemotherapy versus 36.6% for radiotherapy alone). The researchers also observed this trend in 10-year recurrence-free survival among women with a p53 mutation (52.6% for chemoradiation versus 37% for radiation alone). Other mutations common to endometrial cancer, including those with a mismatch repair deficiency (MMRd) or mutation in the POLE gene, did not receive any additional benefit from adjuvant chemotherapy.
The study not only demonstrates benefits to both 10-year overall survival and recurrence-free survival for women with high-risk endometrial cancer who receive adjuvant chemoradiotherapy but also highlights a particular benefit to women with p53 abnormal cancers. These findings underscore the potential of molecular screening in diagnostics and treatment planning.
Sources: J Clin Oncol, World J Surg, Lancet, Lancet Oncol