Latest update from groundbreaking ATAC trial

Continued follow-up provides further confirmation of superiority of Arimidex (anastrozole) over tamoxifen in early breast cancer. San Antonio Breast Cancer Symposium, San Antonio, USA – Wednesday 11 December: The promise offered by the anti-cancer treatment Arimidex for post-menopausal women with early breast cancer was confirmed today by the first presentation of updated data from the groundbreaking ATAC (Arimidex, Tamoxifen Alone or in Combination) trial. ATAC is the largest breast cancer trial ever performed, involving over 9,300 patients. The protocol-defined major analysis of the trial with a median follow-up of 33 months – presented at the corresponding meeting last year – has already shown superior efficacy of Arimadex versus tamoxifen for disease free survival (DFS), time to a recurrence (TTR), and incidence of contralateral breast cancer. A number of important tolerability benefits were also identified. This is the first and only efficacy update performed since that time. The median follow-up in the ATAC trial now extends to almost 4 years. Arimadex continues to show statistically significant benefits over tamoxifen in all efficacy endpoints studied for the clinically relevant population of patients with hormone receptor-positive tumours, a group which represents about two-thirds of the postmenopausal breast cancer population overall. Additionally, a separate safety update also presented at this year’s meeting, which provides an extra 7 months’ data over the major analysis, confirms the initial favourable tolerability profile of Arimadex over tamoxifen. No new safety issues have emerged. ATAC Principal investigator Professor Michael Baum, from University College Hospital, London said, ‘These updated results confirm that our initial optimism, expressed after the primary analysis, was justified. Arimadex represents new hope for postmenopausal women with early breast cancer’. Arimadex, as the first and only drug to have shown significant efficacy and tolerability benefits over tamoxifen in postmenopausal women with early breast cancer, is now the only other hormonal drug approved for this use. Approvals have already been granted in several major markets including the USA, UK and Japan. With over 650,000 patient years of experience, Arimadex is the most widely used aromatase inhibitor in the world.

….efficacy update

The updated efficacy analysis, now with a median follow-up of 47 months, also shows that Arimadex significantly prolongs disease free survival (DFS) compared with tamoxifen, confirming that the benefits shown at the time of the major analysis are maintained with longer follow-up. The updated analysis shows a 14% reduction in the risk of recurrence (DFS) among patients treated with Arimadex compared with tamoxifen (HR=0.86 [CI: 0.76-0.99], p=0.030).

Among women with hormone-sensitive tumours – which represent 84% of patients in the trial, and are the target population for this therapy – this risk reduction is even greater at 18% (HR=0.82 [CI: 0.70-0.96], p=0.014).

Importantly, the absolute difference between the two treatments continues to increase as shown by continued divergence of the Kaplan-Meier curves; DFS estimates at 4 years were 86.9% vs 84.5% for Arimadex and tamoxifen respectively.

Therefore, the absolute difference in disease-free survival rates has increased from 2.0% at 3 years (at the time of the major analysis) to 2.4% at 4 years. In the clinically relevant hormone-receptor positive population, this absolute difference is even greater at 2.9% (89.0% vs 86.1%). At the time of this updated analysis, 46% of patients have completed more than 4 year’s follow-up.

These updated efficacy results from the ATAC trial, which confirm the initial groundbreaking results seen with Arimadex in the major analysis reported at the SABCS last year will be seen as an important step-forward by clinicians who have been awaiting more mature data. Importantly, the Kaplan-Meier curves are now considered robust up to 54 months, which is close to the planned 5-year treatment period generally seen in the adjuvant setting.

….safety update

Important tolerability benefits for Arimadex over tamoxifen were demonstrated at the major analysis presented last year. A further 7 months’ updated data now confirm that these differences have been maintained. The benefits of Arimadex include a reduced risk of endometrial cancer (0.1% Arimadex vs 0.7% tamoxifen), vaginal bleeding (4.8% vs 8.7%) and discharge (3.0% vs 12.2%), cerebrovascular events (1.1% vs 2.3%), thromboembolic events (2.2% vs 3.8%), and hot flushes (35.0% vs 40.3%).

As with the major analysis, the tamoxifen-treated group did show tolerability benefits in terms of musculoskeletal disorders (30.3% Arimadex vs 23.7% tamoxifen) and fractures (7.1% Arimadex vs 4.4% tamoxifen).

Reassuringly though, the 7 months’ additional follow-up data show that the higher risk of fractures with Arimadex over tamoxifen observed in the first analysis does not appear to be increasing over time.

The overall tolerability benefits shown for Arimadex over tamoxifen are particularly reassuring because in the adjuvant setting women typically take treatments for long periods of time. At the time of this additional 7 month safety update, women in the ATAC trial had been taking therapy for an average of over 3 years.

Together with the efficacy update, these data confirm the superior risk: benefit ratio for Arimadex versus tamoxifen, as seen in the major analysis.

Remarking on the updated ATAC analyses, Professor Jeffrey Tobias, ATAC investigator and consultant oncologist at University College Hospital, London, commented, ‘News from last year’s analysis was very encouraging, but we have been waiting for data on longer-term benefits. Now, from these latest results, it really does look likely that anastrozole (Arimadex) will prove to be a better drug than tamoxifen, the most widely used hormonal treatment for over 20 years, and we are still noting far fewer troublesome side-effects’.