DATA Trial: Who Will Benefit From AI Treatment Beyond 5 Years?

Final results from the phase 3 DATA trial indicate that extending AI treatment beyond 5 years of sequential therapy does not benefit all postmenopausal patients with HR-positive breast cancer, but some patients do derive a benefit.3 

This trial ( Identifier: NCT00301457) was designed to examine different durations of AI treatment in postmenopausal patients with HR-positive breast cancer who were free of disease after 2 to 3 years of treatment with tamoxifen. 

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The patients were randomly assigned to 3 years of treatment with anastrozole or 6 years of anastrozole therapy. The intent-to-treat analysis included 827 patients in the 6-year arm and 833 patients in the 3-year arm. 

The study’s primary endpoint was adapted DFS (aDFS), which was defined as DFS from 3 years after randomization onward. There was no significant difference in 10-year aDFS between the 6-year treatment arm and the 3-year treatment arm — 69.1% and 66.0%, respectively (HR, 0.86; 95% CI, 0.72-1.01; P =.073). 

Vivianne C.G. Tjan-Heijnen, MD, PhD

Similarly, there was no significant difference in adapted OS (aOS) between the arms. The 10-year aOS rate was 80.9% in the 6-year arm and 79.2% in the 3-year arm (hazard ratio, 0.93; 95% CI, 0.75-1.16; P =.53).

“We cannot recommend extending aromatase inhibition beyond 5 years of sequential therapy in all postmenopausal women with hormone receptor-positive breast cancer,” said study presenter Vivianne C.G. Tjan-Heijnen, MD, PhD, of Maastricht University Medical Centre in the Netherlands. “It may, however, be considered in subgroups of patients.”

In a subgroup analysis, the researchers found that patients whose tumors were ER-positive and progesterone receptor (PR)-positive benefited from extended treatment with anastrozole. In this group, the 10-year aDFS rate was 70.8% in the 6-year arm and 64.4% in the 3-year arm (hazard ratio, 0.77; 95% CI, 0.63-0.93; P =.018). 

Patients with node-positive, ER-positive, and PR-positive disease also benefited from extended treatment. The 10-year aDFS rate was 68.7% in the 6-year arm and 60.7% in the 3-year arm (hazard ratio, 0.74; 95% CI, 0.59-0.93; P =.011).

Patients who had tumors measuring 2 cm or larger as well as node-positive, ER-positive, and PR-positive disease benefited from extended treatment as well. The 10-year aDFS rate was 70.0% in the 6-year arm and 56.4% in the 3-year arm (hazard ratio, 0.64; 95% CI, 0.47-0.88; P =.005).

However, there was no significant improvement in the 10-year aOS rate in any of these subgroups. Nevertheless, the improvements in aDFS “can be considered as clinically very relevant,” Dr Tjan-Heijnen said in an interview.

Dr Del Mastro, the discussant for this study, noted that these results differ from results of the GIM4 trial.7 In GIM4, patients who had received 2-3 years of treatment with tamoxifen had a significant improvement in DFS when they went on to receive letrozole for 5 years rather than 2-3 years (hazard ratio, 0.78, 95% CI 0.65-0.93; P =.006).

Dr Del Mastro said the significant DFS improvement in GIM4 and the numeric aDFS improvement in the DATA trial support extending AI therapy for certain patients. She suggested that the Breast Cancer Index or the CTS5 Calculator can be used to predict which patients will benefit from extended AI treatment.

METEORA-II Trial: VEX Improves PFS, TTF and Increases Toxicity 

Results from the phase 2 METEORA-II trial suggest an all-oral metronomic chemotherapy regimen can significantly improve time-to-treatment failure (TTF) and progression-free survival (PFS), compared with single-agent paclitaxel.4 However, the metronomic regimen is associated with an increase in toxicity. 

“Although there is no universally accepted definition, metronomic chemotherapy is the chronic administration of chemotherapy at low, minimally toxic doses on a frequent schedule of administration, with no prolonged drug-free breaks, as opposed to the schedule of traditional or standard chemotherapy usually given at ‘maximum tolerated dose’ or MTD,” study presenter Elisabetta Munzone, MD, of Istituto Europeo di Oncologia in Milan, Italy, explained in an interview.

Elisabetta Munzone, MD

Dr Munzone and colleagues conducted the METEORA-II trial ( Identifier: NCT02954055) to compare the metronomic chemotherapy regimen with paclitaxel as first- or second-line therapy in patients with ER-positive, HER2-negative metastatic breast cancer. Paclitaxel was given at 90 mg/m2 on days 1, 8, and 15 of a 4-week cycle. 

The metronomic regimen consisted of vinorelbine, cyclophosphamide, and capecitabine (VEX). Vinorelbine was given at 40 mg on days 1, 3, and 5 every week. Cyclophosphamide was given at 50 mg daily. Capecitabine was given at 500 mg 3 times per day.

There were 133 patients who received study treatment and were evaluable for efficacy and safety — 63 patients in the paclitaxel arm and 70 in the VEX arm.

Results showed that VEX significantly improved TTF and PFS. The median TTF was 8.3 months with VEX and 5.7 months with paclitaxel (hazard ratio, 0.61; 95% CI, 0.42-0.88; P =.008). The median PFS was 11.1 months and 6.9 months, respectively (hazard ratio, 0.67; 95% CI, 0.46-0.96). 

On the other hand, there was no significant difference in OS between the arms. The median OS was 29.5 months in the VEX arm and 33.7 months in the paclitaxel arm (hazard ratio, 0.98; 95% CI, 0.59-1.63). 

Despite the lack of OS improvement, the improvements in TTF and PFS suggest that metronomic VEX could be considered as a valid option in this patient population, according to Dr Munzone. 

However, the discussant for this study said the VEX regimen may only be suitable for certain patients, due to the toxicity burden. Grade 3 or higher targeted adverse events occurred in 42.9% of patients in the VEX arm and 28.6% of patients in the paclitaxel arm.

“[B]ecause the toxicity burden is quite significant … and because we do not see a prolongation of survival, I don’t think this is a regimen that’s suitable for most patients,” said discussant Shom Goel, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, Australia. “There might be select cases where it is suitable.”

He added that an important question from this study is whether the efficacy seen with VEX was due to its metronomic schedule or because it is a 3-drug combination that was compared with single-agent chemotherapy. 

Disclosures: The TROPiCS-02 trial was sponsored by Gilead Sciences. The GIM2 trial was sponsored by Bristol-Myers Squibb, Pharmacia, and Dompè Biotec. The DATA trial was sponsored by AstraZeneca. METEORA-II was sponsored by ETOP IBCSG Partners Foundation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures. 


1. Rugo HS, Bardia A, Marmé F, et al. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). Presented at ESMO 2022; September 9-13, 2022. Abstract LBA76.

2. Del Mastro L, Poggio F, Blondeaux E, et al. Dose-dense adjuvant chemotherapy in early-stage breast cancer patients: End-of-study results from a randomised, phase III trial of the Gruppo Italiano Mammella (GIM). Presented at ESMO 2022; September 9-13, 2022. Abstract 134O.

3. Tjan-Heijnen VCG, Lammers SWM, Geurts SME, et al. Extended adjuvant aromatase inhibition after sequential endocrine therapy: Final results of the phase III DATA trial. Presented at ESMO 2022; September 9-13, 2022. Abstract 133O.

4. Munzone E, Regan MM, Cinieri S, et al. A randomized phase II trial of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) vs weekly paclitaxel (P) as first- or second-line treatment in patients (pts) with ER+/HER2- metastatic breast cancer (MBC): The METEORA-II trial (IBCSG 54-16). Presented at ESMO 2022; September 9-13, 2022. Abstract 216MO.

5. Rugo HS, Bardia A, Marme F, et al. Sacituzumab govitecan in hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer. J Clin Oncol. Published online August 26, 2022. doi:10.1200/JCO.22.01002

6. Del Mastro L, De Placido S, Bruzzi P, et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015;385(9980):1863-72. doi:10.1016/S0140-6736(14)62048-1

7. Del Mastro L, Mansutti  M , Bisagni G, et al. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(10):1458-1467. doi:10.1016/S1470-2045(21)00352-1