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NEW ORLEANS – Adding the anti-HER2 antibody trastuzumab to a standard chemotherapy regimen produced markedly improved responses among patients with an advanced stage or recurrent uterine serous carcinoma that also overexpressed the HER2/neu cell receptor protein in a controlled, multicenter, phase 2 study with 58 evaluable patients.
The 30 patients who received trastuzumab along with carboplatin plus paclitaxel had a median progression-free survival of 12.6 months compared with 8.0 months among the 28 control patients who received only carboplatin plus paclitaxel, a hazard reduction of 56% with trastuzumab that was statistically significant (P = .0052), Alessandro D. Santin, MD, said at the annual meeting of the Society of Gynecologic Oncology.
In the subgroup of 41 patients with advanced (not recurrent) uterine serous carcinoma (USC) the incremental difference in median progression-free survival among patients treated with trastuzumab was 8.6 months, based on a 17.9-month duration in the 20 patients who received trastuzumab and 9.3 months in 20 control patients on chemotherapy only (P = .013).
“We’ll push to have the trastuzumab, carboplatin, and paclitaxel regimen in the guidelines” for treating patients with USC that overexpresses HER2/neu, agreed Amanda N. Fader, MD, director of gynecologic oncology at Johns Hopkins Medicine in Baltimore and lead author on the study reported by Dr. Santin.
Shortly after Dr. Santin’s report at the meeting, the results appeared in an article published online March 27 in Journal of Clinical Oncology.
The phase 2 trial ran at 11 U.S. centers during 2011-2016, and randomized 61 patients with stage III or IV or recurrent USC and high HER2 protein expression measured by immunohistochemistry and amplification of the HER2 gene shown by fluorescence in situ hybridization. The researchers collected data from 58 treated patients. Among the 17 patients with recurrent disease, those who received trastuzumab had a median progression-free survival of 9.2 months compared with 6.0 months in the controls, a hazard reduction of 86% with trastuzumab that was statistically significant (P = .0029). The addition of trastuzumab to carboplatin and paclitaxel was well tolerated.
The greatest benefit from the trastuzumab plus chemotherapy regimen might occur when used as first-line treatment, Dr. Santin suggested. He expressed interest in running a second study to validate the current findings, and a new study that would combine a second antibody directed against HER2, pertuzumab (Perjeta) with trastuzumab, carboplatin, and paclitaxel.
A key factor in making the trastuzumab plus chemotherapy regimen more widely available to USC patients would be routinely screening these patients for high levels of HER2/neu expression immediately after USC is diagnosed. “At Yale and Johns Hopkins this testing is done on all USC patients. That’s not standard care everywhere, but it should be based on these data,” Dr. Santin said in an interview.
SOURCE: Fader A et al. Abstract 22. J Clin Oncol. 2018 Mar 27. doi: 10.1200/JCO.2017.76.5966.
NEW ORLEANS – Adding the anti-HER2 antibody trastuzumab to a standard chemotherapy regimen produced markedly improved responses among patients with an advanced stage or recurrent uterine serous carcinoma that also overexpressed the HER2/neu cell receptor protein in a controlled, multicenter, phase 2 study with 58 evaluable patients.
The 30 patients who received trastuzumab along with carboplatin plus paclitaxel had a median progression-free survival of 12.6 months compared with 8.0 months among the 28 control patients who received only carboplatin plus paclitaxel, a hazard reduction of 56% with trastuzumab that was statistically significant (P = .0052), Alessandro D. Santin, MD, said at the annual meeting of the Society of Gynecologic Oncology.
In the subgroup of 41 patients with advanced (not recurrent) uterine serous carcinoma (USC) the incremental difference in median progression-free survival among patients treated with trastuzumab was 8.6 months, based on a 17.9-month duration in the 20 patients who received trastuzumab and 9.3 months in 20 control patients on chemotherapy only (P = .013).
“We’ll push to have the trastuzumab, carboplatin, and paclitaxel regimen in the guidelines” for treating patients with USC that overexpresses HER2/neu, agreed Amanda N. Fader, MD, director of gynecologic oncology at Johns Hopkins Medicine in Baltimore and lead author on the study reported by Dr. Santin.
Shortly after Dr. Santin’s report at the meeting, the results appeared in an article published online March 27 in Journal of Clinical Oncology.
The phase 2 trial ran at 11 U.S. centers during 2011-2016, and randomized 61 patients with stage III or IV or recurrent USC and high HER2 protein expression measured by immunohistochemistry and amplification of the HER2 gene shown by fluorescence in situ hybridization. The researchers collected data from 58 treated patients. Among the 17 patients with recurrent disease, those who received trastuzumab had a median progression-free survival of 9.2 months compared with 6.0 months in the controls, a hazard reduction of 86% with trastuzumab that was statistically significant (P = .0029). The addition of trastuzumab to carboplatin and paclitaxel was well tolerated.
The greatest benefit from the trastuzumab plus chemotherapy regimen might occur when used as first-line treatment, Dr. Santin suggested. He expressed interest in running a second study to validate the current findings, and a new study that would combine a second antibody directed against HER2, pertuzumab (Perjeta) with trastuzumab, carboplatin, and paclitaxel.
A key factor in making the trastuzumab plus chemotherapy regimen more widely available to USC patients would be routinely screening these patients for high levels of HER2/neu expression immediately after USC is diagnosed. “At Yale and Johns Hopkins this testing is done on all USC patients. That’s not standard care everywhere, but it should be based on these data,” Dr. Santin said in an interview.
SOURCE: Fader A et al. Abstract 22. J Clin Oncol. 2018 Mar 27. doi: 10.1200/JCO.2017.76.5966.
NEW ORLEANS – Adding the anti-HER2 antibody trastuzumab to a standard chemotherapy regimen produced markedly improved responses among patients with an advanced stage or recurrent uterine serous carcinoma that also overexpressed the HER2/neu cell receptor protein in a controlled, multicenter, phase 2 study with 58 evaluable patients.
The 30 patients who received trastuzumab along with carboplatin plus paclitaxel had a median progression-free survival of 12.6 months compared with 8.0 months among the 28 control patients who received only carboplatin plus paclitaxel, a hazard reduction of 56% with trastuzumab that was statistically significant (P = .0052), Alessandro D. Santin, MD, said at the annual meeting of the Society of Gynecologic Oncology.
In the subgroup of 41 patients with advanced (not recurrent) uterine serous carcinoma (USC) the incremental difference in median progression-free survival among patients treated with trastuzumab was 8.6 months, based on a 17.9-month duration in the 20 patients who received trastuzumab and 9.3 months in 20 control patients on chemotherapy only (P = .013).
“We’ll push to have the trastuzumab, carboplatin, and paclitaxel regimen in the guidelines” for treating patients with USC that overexpresses HER2/neu, agreed Amanda N. Fader, MD, director of gynecologic oncology at Johns Hopkins Medicine in Baltimore and lead author on the study reported by Dr. Santin.
Shortly after Dr. Santin’s report at the meeting, the results appeared in an article published online March 27 in Journal of Clinical Oncology.
The phase 2 trial ran at 11 U.S. centers during 2011-2016, and randomized 61 patients with stage III or IV or recurrent USC and high HER2 protein expression measured by immunohistochemistry and amplification of the HER2 gene shown by fluorescence in situ hybridization. The researchers collected data from 58 treated patients. Among the 17 patients with recurrent disease, those who received trastuzumab had a median progression-free survival of 9.2 months compared with 6.0 months in the controls, a hazard reduction of 86% with trastuzumab that was statistically significant (P = .0029). The addition of trastuzumab to carboplatin and paclitaxel was well tolerated.
The greatest benefit from the trastuzumab plus chemotherapy regimen might occur when used as first-line treatment, Dr. Santin suggested. He expressed interest in running a second study to validate the current findings, and a new study that would combine a second antibody directed against HER2, pertuzumab (Perjeta) with trastuzumab, carboplatin, and paclitaxel.
A key factor in making the trastuzumab plus chemotherapy regimen more widely available to USC patients would be routinely screening these patients for high levels of HER2/neu expression immediately after USC is diagnosed. “At Yale and Johns Hopkins this testing is done on all USC patients. That’s not standard care everywhere, but it should be based on these data,” Dr. Santin said in an interview.
SOURCE: Fader A et al. Abstract 22. J Clin Oncol. 2018 Mar 27. doi: 10.1200/JCO.2017.76.5966.
REPORTING FROM SGO 2018
Key clinical point: Trastuzumab plus chemotherapy improved progression-free survival in a phase 2 study.
Major finding: Median progression-free survival was 12.6 months with trastuzumab and 8.0 months in controls.
Study details: A multicenter, phase 2 study that enrolled 58 evaluable patients.
Disclosures: Trastuzumab was provided at no charge by Genentech. Dr. Santin and Dr. Fader had no relevant disclosures.
Source: Fader A et al. Abstract 22. J Clin Oncol. 2018 Mar 27. doi: 10.1200/JCO.2017.76.5966)
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The biological relevance of HER2 amplification has been clearly established in the results from this and other studies. But we must keep in kind that the results reported by Dr. Santin have applicability to a subset of a subset of patients. Specifically, about 10% of endometrial cancers are uterine serous carcinoma (USC) (although they account for roughly 40% of deaths among endometrial cancer patients), about half of USC patients show a high level of HER2/neu expression by immunohistochemistry, and about 60% of these high-expressing USC also have HER2 gene amplification. The study presented by Dr. Santin ran at 11 centers for 5.5 years and enrolled just 61 patients, fewer than the planned enrollment target of 100 patients.
Michael A. Bookman, MD , is director of gynecologic oncology therapeutics at the Permanente Medical Group in San Francisco. He has been an adviser to AstraZeneca, Bayer, Clovis, Merck, Pfizer, and Tesaro, and he has participated in trials funded by Abbvie, Genentech, Immunogen, Mateon, and Roche. He made these comments as designated discussant for the study.