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Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

ABSTRACT: BACKGROUND:Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity. METHODS:HER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression. RESULTS:Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01-5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5-53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population. CONCLUSIONS:In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted.

SUBMITTER: Al-Shamsi HO

PROVIDER: S-EPMC4963369 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

Al-Shamsi Humaid O HO Fahmawi Yazan Y Dahbour Ibrahim I Tabash Aziz A Rogers Jane E JE Mares Jeannette Elizabeth JE Blum Mariela A MA Estrella Jeannelyn J Matamoros Aurelio A Sagebiel Tara T Devine Catherine E CE Badgwell Brian D BD Lin Quan D QD Das Prajnan P Ajani Jaffer A JA

Journal of gastrointestinal oncology 20160801 4

<h4>Background</h4>Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity.<h4>Methods</h4>HER2-overexp ...[more]

PMID: 27563438

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Project description:BackgroundTrastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively).MethodsThe ROP Study was a single-arm, multicenter, international continuation trial of H in patients who had previously completed a global Roche-sponsored trial with H therapy, had stable disease, and were receiving H at the end of the lead-in trial. Patients with chronic heart failure during the lead-in trial could be included following a risk-benefit analysis. The primary objectives were to provide H therapy to patients with HER2-overexpressing locally advanced/metastatic breast or gastric/GEJ cancer at the end of the lead-in study, and to follow the long-term outcomes and long-term overall safety in these patients.ResultsTwenty-five of 69 patients enrolled in the ROP Study received long-term H therapy (19 breast cancer and 6 gastric/GEJ cancer). The median duration of H treatment for patients with breast cancer was 8 years 7 months, and 5 years 2 months for patients with gastric/GEJ cancer. The cardiac status of the patients remained stable over time, with no serious cardiac adverse events or marked changes in left ventricular ejection fraction (LVEF). The median overall worst LVEF measurement was 57.0%, and no patients experienced an LVEF of < 45% (range 47-63%). There were no serious adverse events related to study treatment.ConclusionsThese results suggest that H has an acceptable safety profile and was well tolerated in patients who received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively). Further investigation and reporting of long-term H therapy would be valuable.Trial registrationThis study was retrospectively registered on March 24, 2016 with Clinicaltrials.gov, number NCT02721641 .

Project description:BackgroundIn patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.MethodsWe randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.ResultsThe median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.ConclusionsIn patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).

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Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

Publications

Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience.

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