User login
, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.
The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).
Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.
Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.
Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).
At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.
“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”
In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”
Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.
“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
Study details
The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.
The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.
A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.
Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.
The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.
SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.
, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.
The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).
Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.
Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.
Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).
At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.
“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”
In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”
Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.
“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
Study details
The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.
The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.
A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.
Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.
The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.
SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.
, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.
The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).
Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.
Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.
Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).
At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.
“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”
In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”
Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.
“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
Study details
The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.
The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.
A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.
Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.
The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.
SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.
FROM LANCET ONCOLOGY