BrighTNess Shines Light On Best Neoadjuvant Regimen For Triple-Negative Breast Cancer

Patients with triple-negative breast cancer benefit from the addition of carboplatin, but not veliparib, to neoadjuvant chemotherapy

medwireNews: The likelihood of a pathological complete response (pCR) in patients with triple-negative breast cancer is increased by the addition of carboplatin to neoadjuvant chemotherapy, research suggests.

However, results from the BrighTNess trial failed to show additional benefit when the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib was also included in the regimen, report Sibylle Loibl, from the German Breast Group in Neu-Isenburg, Germany, and co-investigators.

“The BrighTNess findings provide important information that supports the inclusion of carboplatin as a component of a standard neoadjuvant regimen in patients with stage II–III triple-negative breast cancer for whom a major goal of treatment is achieving clinical and pathological response in the breast and regional nodes”, the researchers write in The Lancet Oncology.

“These findings also support inclusion of carboplatin in the control regimen for subsequent studies of investigational agents (ie, immune checkpoint inhibitors) being assessed in the neoadjuvant setting for this disease”, they say.

The phase III trial included 634 patients with stage II–III breast cancer who were candidates for potentially curative surgery; all had no or minimal expression of oestrogen, progesterone or HER2 receptors, and no HER2 gene amplification.

The patients were randomly assigned to receive one of three regimens: weekly paclitaxel 80 mg/m2 for 12 weeks plus double placebo; paclitaxel plus four cycles of carboplatin given to an area under the curve of 6 mg/mL per minute every 3 weeks and placebo; or paclitaxel plus carboplatin and veliparib 50 mg twice daily.

All patients were then given a second stage of treatment consisting of four cycles of doxorubicin 60 mg/m2 and cylophosophamide 600 mg/m2 every 2–3 weeks, the team explains.

Overall, pCR was achieved by 31%, 58% and 53% of the paclitaxel, paclitaxel plus carboplatin, and paclitaxel plus carboplatin and veliparib treatment arms, respectively. While paclitaxel, carboplatin plus veliparib offered a significant improvement in this endpoint compared with paclitaxel alone, the triple regimen was only statistically comparable to the paclitaxel plus carboplatin regimen.

Patients given carboplatin with or without veliparib had a significantly higher rate of both grade 3 or 4 treatment-emergent adverse events (71 and 68 vs 15%) and serious adverse events (9 and 10 vs 3%) than those treated with paclitaxel alone.

Patients given carboplatin plus veliparib or carboplatin alone alongside paclitaxel were also more likely to discontinue paclitaxel than those using paclitaxel only (11 and 6 vs 3%), and to require a dose delay or reduction.

Nevertheless, the researchers emphasize that over 88% of patients in all three treatment arms received at least 11 weekly doses of paclitaxel and over 90% of those randomly assigned to receive carboplatin received their full scheduled doses.

And the addition of veliparib to paclitaxel plus carboplatin was associated with an increase in the rate of grade 3–4 anaemia and thrombocytopenia but had “no discernible effect” on nonhaematological side effects.

Acknowledging the increased toxicities with carboplatin and the “known heterogeneity” of triple-negative breast cancer, the researchers conclude that “identification of predictive biomarkers to better define the subsets of patients who benefit the most from the addition of carboplatin would be helpful.”

They add: “Pretreatment core biopsies for exploratory studies were mandatory in this trial, and the initial tests to address this important issue are underway”.

The author of an accompanying comment agrees that better identification of patients likely to respond to carboplatin may further improve the rate of pCR and minimise side effects.

Giuseppe Curigliano, from the University of Milan in Italy, notes, however, that the trial did not shed light on “whether the addition of a single, potent PARP inhibitor to platinum monotherapy in the neoadjuvant setting could improve the proportion of patients achieving a pathological complete response, or what optimal dose and schedule should be used in future trials testing these inhibitors.”

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

References

medwireNews: The likelihood of a pathological complete response (pCR) in patients with triple-negative breast cancer is increased by the addition of carboplatin to neoadjuvant chemotherapy, research suggests.

However, results from the BrighTNess trial failed to show additional benefit when the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib was also included in the regimen, report Sibylle Loibl, from the German Breast Group in Neu-Isenburg, Germany, and co-investigators.

“The BrighTNess findings provide important information that supports the inclusion of carboplatin as a component of a standard neoadjuvant regimen in patients with stage II–III triple-negative breast cancer for whom a major goal of treatment is achieving clinical and pathological response in the breast and regional nodes”, the researchers write in The Lancet Oncology.

“These findings also support inclusion of carboplatin in the control regimen for subsequent studies of investigational agents (ie, immune checkpoint inhibitors) being assessed in the neoadjuvant setting for this disease”, they say.

The phase III trial included 634 patients with stage II–III breast cancer who were candidates for potentially curative surgery; all had no or minimal expression of oestrogen, progesterone or HER2 receptors, and no HER2 gene amplification.

The patients were randomly assigned to receive one of three regimens: weekly paclitaxel 80 mg/m2 for 12 weeks plus double placebo; paclitaxel plus four cycles of carboplatin given to an area under the curve of 6 mg/mL per minute every 3 weeks and placebo; or paclitaxel plus carboplatin and veliparib 50 mg twice daily.

All patients were then given a second stage of treatment consisting of four cycles of doxorubicin 60 mg/m2 and cylophosophamide 600 mg/m2 every 2–3 weeks, the team explains.

Overall, pCR was achieved by 31%, 58% and 53% of the paclitaxel, paclitaxel plus carboplatin, and paclitaxel plus carboplatin and veliparib treatment arms, respectively. While paclitaxel, carboplatin plus veliparib offered a significant improvement in this endpoint compared with paclitaxel alone, the triple regimen was only statistically comparable to the paclitaxel plus carboplatin regimen.

Patients given carboplatin with or without veliparib had a significantly higher rate of both grade 3 or 4 treatment-emergent adverse events (71 and 68 vs 15%) and serious adverse events (9 and 10 vs 3%) than those treated with paclitaxel alone.

Patients given carboplatin plus veliparib or carboplatin alone alongside paclitaxel were also more likely to discontinue paclitaxel than those using paclitaxel only (11 and 6 vs 3%), and to require a dose delay or reduction.

Nevertheless, the researchers emphasize that over 88% of patients in all three treatment arms received at least 11 weekly doses of paclitaxel and over 90% of those randomly assigned to receive carboplatin received their full scheduled doses.

And the addition of veliparib to paclitaxel plus carboplatin was associated with an increase in the rate of grade 3–4 anaemia and thrombocytopenia but had “no discernible effect” on nonhaematological side effects.

Acknowledging the increased toxicities with carboplatin and the “known heterogeneity” of triple-negative breast cancer, the researchers conclude that “identification of predictive biomarkers to better define the subsets of patients who benefit the most from the addition of carboplatin would be helpful.”

They add: “Pretreatment core biopsies for exploratory studies were mandatory in this trial, and the initial tests to address this important issue are underway”.

The author of an accompanying comment agrees that better identification of patients likely to respond to carboplatin may further improve the rate of pCR and minimise side effects.

Giuseppe Curigliano, from the University of Milan in Italy, notes, however, that the trial did not shed light on “whether the addition of a single, potent PARP inhibitor to platinum monotherapy in the neoadjuvant setting could improve the proportion of patients achieving a pathological complete response, or what optimal dose and schedule should be used in future trials testing these inhibitors.”

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

References

Loibl S, O’Shaughnessy J, Untch M, et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neodjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol; Advance online publication 28 February 2018.
DOI: https://doi.org/10.1016/S1470-2045(18)30111-6

Curigliano G. Addition of platinum salts to neoadjuvant chemotherapy in triple-negative breast cancer: a new standard of care? Lancet Oncol; Advance online publication 28 February 2018.
DOI: https://doi.org/10.1016/S1470-2045(18)30129-3

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group