Combined therapy may help treat, prevent recurrence in cervical cancer

Researchers of the current trial note that outcomes for cervical cancer have improved but that “up to 30% of patients will relapse and die within 5 years.” This alone makes improving cervical cancer treatment a critical area of study.

This trial was a randomized phase 3 trial that included 32 medical centers in five different countries. Participants were ages 18 or older and had locally advanced cervical cancer. Researchers recruited 500 participants, with 47 participants lost to follow-up.

The researchers randomly assigned participants to either the standard treatment group or the intervention group.

The standard treatment group received a weekly treatment of cisplatin-based chemoradiotherapy. This treatment involved weekly intravenous cisplatin and two types of radiation therapy: external beam radiation therapy (EBRT) and brachytherapy. The median treatment time for the radiation was 45 days.

The intervention group received six weeks of induction chemotherapy followed by the same chemoradiotherapy treatment as the other group. both groups showed high adherence to the treatment. The median follow-up time with participants was just over five and a half years.

Overall, the outcomes were better for the group that received the induction chemotherapy. This group had a higher rate of five-year progression-free survival and five-year overall survival.

Study author Mary McCormack, PhD, with the University College London Hospitals NHS Foundation Trust, noted the key highlights of the research to Medical News Today:

“The trial showed that a short course of chemotherapy (weekly for six weeks) delivered before the current standard chemoradiation led to an 8% (80% vs. 72%) improvement in the overall survival rate at five years. Also, more women were alive at five years without cancer recurrence in the group that had the additional chemotherapy (72% vs. 64%).”

In addition, there was better timing between participants’ treatment and their next anticancer therapy in the intervention group.

Local or pelvic relapse was slightly higher in the induction chemotherapy group at 11% compared to 9% in the chemoradiotherapy-only group. However, distant relapse was only 7% in the induction chemotherapy group and 12% in the chemoradiotherapy-only group.

Based on this study’s results, this specific treatment combination could increase cervical cancer survival rates. The researchers note that other clinical trials could test this treatment regimen. They also note that the data supports the idea that the delay in chemoradiotherapy to do induction chemotherapy first overall does not harm clinical outcomes, as long as there is careful timing coordination.

Diana Pearre, MD, a board certified gynecologic oncologist at The Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center in Burbank, CA, who was not involved in the study, noted the following clinical implications to MNT:

“Especially in women, where even seeing a radiation oncologist to start radiation therapy can be another obstacle, starting them on induction chemotherapy not only is a feasible strategy, as evidence by earlier studies, but is a wise one, as evidenced by this study. This study, if adopted widely, would be offering a paradigm shifting alternative that many will have trouble adopting.”

“However, it will be pivotal for us, as clinicians, to examine which group in this locally advanced benefit can benefit most from this approach,” she added.

What about risks?

It’s also important to weigh the potential risks as well. In the current trial, 30% of participants in the additional chemotherapy group experienced hematological adverse events, compared to 13% in the standard treatment group. Researchers expected this and recommended carefully monitoring blood counts with this treatment regimen.

In addition, 22% of participants in the induction chemotherapy group experienced grade 3-4 adverse events while receiving the induction chemotherapy.

The results also don’t imply that this protocol should be used in every situation of cervical cancer. Rikki Baldwin, D.O., OB/GYN, Memorial Hermann noted the following:

“Although this study could potentially provide a breakthrough in the successful treatment of cervical cancer, I do not believe it can be used in treatment of all women with cervical cancer. Administering induction chemotherapy could potentially fail, thereby increasing the amount of time that the cancer has to grow and spread.”

“There is still literature that argues for the standard treatment of chemoradiation to provide the most favorable outcomes. The INTERLACE trial confirms the need for shared decision making when determining the best treatment options for cervical cancer,” she added.

This research does have some limitations. First, over 75% of participants were from the U.K., so more data from other countries and more diversity could be helpful.

The researchers acknowledge that their data did not include certain participants with high-risk cervical cancer, and this could have impacted the results. They had specific inclusion criteria, so the results are not necessarily applicable to all types of cervical cancer.

While there were variations in radiation treatment, these variations were similar between the intervention and standard care groups. In addition, more research may be required on the required minimum number of doses of cisplatin, as this could reveal more benefits of combining induction therapy and chemoradiotherapy.

Based on the recruitment size, researchers noted that they could determine a hazard ratio of 0.65 to 0.70 after 192 deaths or more. However, fewer than this number occurred during the study and follow-up. Researchers note that they will publish more overall survival data in the future.

In addition, some study authors reported conflicts of interest in the published results.

Despite these limitations, the results show a potential way to improve clinical outcomes related to cervical cancer and open pathways for further research.

“The drugs used in this study are widely available. Therefore this treatment should be offered to women with cervical cancer that is not amenable to curative surgery (ie. locally advanced disease). The next question will be to explore if adding immunotherapy to this chemotherapy [and] chemoradiation will improve the survival further.”
— Mary McCormack, PhD, study author