Salvage Treatment and Outcomes of Locally Advanced Cervical Cancer after Failed Concurrent Chemoradiation with or without Adjuvant Chemotherapy: Post Hoc Data Analysis from the ACTLACC Trial.

OBJECTIVES: To evaluate the type of salvage treatment and outcomes of patients with locally advanced cervical cancer who failed treatment with concurrent chemoradiation with or without adjuvant chemotherapy. METHODS: This was post hoc analyses of data from the randomized trial which included 259 patients who had FIGO stage IIB-IVA and had either pelvic radiation therapy concurrent with cisplatin followed by observation or paclitaxel plus carboplatin. Data of the patients who failed primary treatment were collected: type of salvage treatments, time to progress after salvage therapy, progression-free (PFS) and overall survivals (OS). RESULTS: After primary treatment, 85 patients had either persistence (36.5%), progression (18.8%), or recurrences (44.7%). The sites of failure were loco/regional in 52.9%, systemic failure in 30.6%, and loco-regional and systemic in 16.5%. Chemotherapy was given in 51.8%, being the sole therapy in 34.1%. Majority were combination agents (31.8%), with paclitaxel/carboplatin as the most common regimen. Radiation to the metastatic sites along with chemotherapy was used in 14.1% whereas palliative radiation therapy or supportive care was used in approximately 10% of each. The median time from the start of salvage treatment to progression was 9.2 months (range 0.2-64.0 months) with median PFS of 11.2 months (95% CI, 7.2-15.3 months). Median overall survival 27.3 months (95% CI, 4.4-69.6 months). CONCLUSIONS: Chemotherapy, either alone or with radiation therapy, was the most common salvage treatment in LACC after failure from primary treatment. The time to progress and PFS were less than 1 year with OS of approximately 2 years.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

OBJECTIVES: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001.