Additional chemotherapy given after standard chemoradiation treatment does not improve survival for women with locally advanced cervical cancer, and is associated with additional side effects, according to results of a phase III international trial.
These long- anticipated findings, to be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, are likely to immediately change practice for early adopters, who had hoped the regimen would reduce distant disease recurrence in patients.
The standard treatment for locally advanced cervical cancer is chemoradiation with cisplatin-based chemotherapy concurrent with radiation.
Yet a significant percentage of patients still relapse and die as a result of distant metastatic disease.
Because carboplatin and paclitaxel chemotherapy after chemoradiation are active initial treatments for the metastatic and relapsed setting and are successfully used as adjuvant therapy for other cancers, some oncologists routinely treat women with locally advanced cervical cancer with the regimen.
However, until now, there has been no evidence from a large phase III study for or against the addition of chemotherapy in this setting.
The phase III OUTBACK trial demonstrated that chemotherapy following chemoradiation did not improve survival over standard chemoradiation alone for patients with locally advanced cervical cancer.
The international trial enrolled 919 patients with locally advanced cervical cancer.
Patients were randomly assigned to receive standard cisplatin-based chemoradiation with or without additional chemotherapy with carboplatin and paclitaxel.
The primary endpoint was OS at 5 years.
The researchers also examined progression-free survival, adverse side effects, and patterns of disease recurrence.
At 5 years, OS was comparable for both groups – 72% versus 71% respectively, for those receiving adjuvant chemotherapy and those receiving standard care.
Also, at 5 years disease had not progressed (progression-free survival, PFS) for 63% of patients who received the additional treatment, compared with 61% who did not.
Patterns of disease recurrence were similar in the two treatment groups.
Serious adverse events (grade 3-5) were experienced by more patients up to 1 year after randomisation – 81% of patients in the adjuvant chemotherapy group compared with 62% in the standard treatment group.
“The study confirms that chemoradiotherapy alone is currently our best possible treatment for women with locally advanced cervical cancer.
Not only is there no benefit with adjuvant chemotherapy, but severe side effects are also increased,” said lead author Linda R. Mileshkin, MD, a medical oncologist at Peter McCallum Cancer Centre in Melbourne, Australia.
“This trial provides clear evidence that the addition of chemotherapy after chemoradiation does not extend survival. The results are immediately practice-changing, showing that this approach should not be used to treat locally advanced cervical cancer. We can now spare our patients the side effects and toxicity that comes with additional chemotherapy,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO.
The researchers plan to complete additional analyses to answer some of the secondary objectives, such as the impact of standard chemoradiation with or without additional chemotherapy on the psycho-sexual health of patients with advanced cervical cancer.