Dataset Information

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

ABSTRACT:

Aim

To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.

Patients and methods

8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac).

Results

At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups.

Conclusion

T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer.

Trial registration

clinicaltrials.gov Identifier NCT00490139.

SUBMITTER: Moreno-Aspitia A

PROVIDER: S-EPMC8103014 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

Moreno-Aspitia Alvaro A Holmes Eileen M EM Jackisch Christian C de Azambuja Evandro E Boyle Frances F Hillman David W DW Korde Larissa L Fumagalli Debora D Izquierdo Miguel A MA McCullough Ann E AE Wolff Antonio C AC Pritchard Kathleen I KI Untch Michael M Guillaume Sébastien S Ewer Michael S MS Shao Zhimin Z Sim Sung Hoon SH Aziz Zeba Z Demetriou Georgia G Mehta Ajay O AO Andersson Michael M Toi Masakazu M Lang Istvan I Xu Binghe B Smith Ian E IE Barrios Carlos H CH Baselga Jose J Gelber Richard D RD Piccart-Gebhart Martine M

European journal of cancer (Oxford, England : 1990) 20210323

<h4>Aim</h4>To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.<h4>Patients and methods</h4>8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, n ...[more]

PMID: 33765513

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Project description:Choice of therapy for breast cancer relies on human epidermal growth factor receptor-2 (HER2) and estrogen receptor α (ER) status. Before randomization in the phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial for HER2-positive disease, HER2 and ER were centrally reviewed by Mayo Clinic (Rochester, MN, and Scottsdale, AZ) for North America and by the European Institute of Oncology (IEO; Milan, Italy) for the rest of world (except China). Discordance rates (local vs. central review) differed between Mayo and IEO. Among locally HER2-positive cases, 5.8 % (Mayo) and 14.5 % (IEO) were centrally HER2 negative. Among locally ER-positive cases, 16.2 % (Mayo) and 4.2 % (IEO) were centrally ER-negative. Among locally ER-negative cases, 3.4 % (Mayo) and 21.4 % (IEO) were centrally ER-positive. We, therefore, performed a ring study to identify features contributing to these differing discordance rates. Mayo and IEO exchanged slides for 25 HER2 and 35 ER locally/centrally discordant cases. Both laboratories performed IHC and FISH for HER2 using the HercepTest(®) and PathVysion HER2 DNA probe kit/HER2/centromere 17 probe mixture. IHC for ER was tested centrally using the monoclonal ER 1D5 antibody (Mayo) or the DAKO cocktail of ER 1D5 and 2.123 antibodies (IEO). Mayo and IEO confirmed the central HER2-negative result in 100 % of 25 cases. Mayo and IEO confirmed the central ER result in 29 (85 %) of 34 evaluable cases. The five Mayo-negative/IEO-positive cases were ER-positive when retested at Mayo using the DAKO ER cocktail. In this ring study, ALTTO ineligibility did not change when HER2 testing was performed by either IEO or Mayo central laboratories. However, a dual antibody ER assay had fewer false-negative test results than an assay with a single antibody, and there was more discordance between the two ER reagents than has been previously reported. Using even slightly different assay methods yielded different results, even between experienced central laboratories.

Project description:PurposeGiven that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation.MethodsAcute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy.ResultsThree hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P < .0001).ConclusionAcute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies.

Dataset Information

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

Aim

Patients and methods

Results

Conclusion

Trial registration

Publications

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

Similar Datasets

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