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Cite this articleWeekly adjuvant paclitaxel improves survival after standard chemotherapy in breast cancer. Nat Rev Clin Oncol 5, 498 (2008). Https://doi.Org/10.1038/ncponc1171
Share this article Get shareable linkFirst-Line Lenvima Plus Keytruda Misses Mark In Endometrial Cancer
For patients with advanced or recurrent endometrial cancer, first-line Lenvima plus Keytruda didn't significantly improve outcomes versus chemotherapy.
First-line Lenvima and Keytruda does not significantly improve outcomes versus chemotherapy in endometrial cancer.
Among patients with advanced or recurrent endometrial cancer (aEC), first-line treatment with Lenvima (lenvatinib) plus Keytruda (pembrolizumab) did not result in statistically significant improvements in survival and progression versus treatment with chemotherapy, researchers have reported.
Researchers published their findings from the phase 3 European Network of Gynecological Oncological Trial (ENGOT)-en9/LEAP-001 study in the Journal of Clinical Oncology.
The Food and Drug Administration (FDA) previously granted the combination regular approval for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in 2021 based on the Study 309/KEYNOTE-775 trial following an accelerated approval that was granted in 2019.
GlossaryMismatch repair deficient: Mismatch repair deficiency, according to the National Cancer Institute, describes cells that have mutations in genes that are involved in correcting mistakes made when DNA is copied, and mismatch repair deficient cells usually have many DNA mutations, which may lead to cancer.
Mismatch repair proficient: When the body's DNA repair system functions as it should.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Overall survival: the time a patient lives, regardless of disease status.
Neoadjuvant: treatment that occurs before the main treatment, such as surgery.
Adjuvant: treatment that occurs after the main treatment.
Cerebrovascular accident: a stroke.
Intracranial hematoma: collection of blood inside the skull.
Pneumonitis: inflammation of the lungs.
Subcutaneous hemorrhage: bleeding under the skin.
"Negative trials are important and may inform practice as much as positive trials. Paclitaxel-carboplatin–containing regimens are standard-of-care initial treatment for advanced endometrial cancer. The [Lenvima plus Keytruda] combination is an effective option in patients with progression on or after previous chemotherapy," noted Journal of Clinical Oncology senior deputy editor Dr. Kathy D. Miller in a contextual supplement published with the study.
Researchers enrolled 842 patients with stage 3 to 4 or recurrent endometrial cancer with no previous chemotherapy or disease progression at least six months after neoadjuvant/adjuvant platinum-based chemotherapy, with 420 patients in the Lenvima and Keytruda arm, including 320 in the pMMR population, and 422 patients in the chemotherapy arm, including 322 in the pMMR population.
As of the final analysis data cutoff of Oct. 2, 2023, the median progression-free survival was 9.6 months among the Lenvima and Keytruda arm versus 10.2 months in the chemotherapy arm in the pMMR population and 12.5 months versus 10.2 months among all patients, according to the study's findings.
Median overall survival was 30.9 months for the Lenvima plus Keytruda arm and 29.4 months in the chemotherapy arm for pMMR patients, and 37.7 months versus 32.1 months for all patients, researchers reported.
Regarding safety, researchers reported that no new safety signals were identified with either treatment regimen in the trial. For patients who received at least one dose of treatment, 98% of patients on the combination arm and 97% on the chemotherapy arm experienced treatment-related side effects of any grade. Notably, grade 3 (severe) to 4 (life-threatening) treatment-related side effects occurring in 76% and 66% of patients, respectively.
Notably, 2% of participants in the Lenvima plus Keytruda arm and than 1% of those on the chemotherapy arm died due to treatment-related side effects, researchers reported. The causes of death for the Lenvima plus Keytruda group were listed as cerebrovascular accident (two patients), large intestine perforation, death (general disorder), cerebral hemorrhage, hemorrhagic stroke, intracranial hematoma, acute respiratory failure, pneumonitis and subcutaneous hemorrhage (one each); and for the chemotherapy group, it was listed as pneumonia aspiration and sepsis (one each).
"This phase 3 trial of [Lenvima plus Keytruda] versus paclitaxel-carboplatin [chemotherapy] did not meet the prespecified statistical criteria for [progression-free survival] or [overall survival] as first-line treatment for patients with [mismatch repair-proficient (pMMR)] aEC. … Our findings underscore the challenges of replacing rather than adding to the entrenched standard of care, paclitaxel-carboplatin, in aEC in the first-line setting," researchers concluded.
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Reference"First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial" by Dr. Christian Marth et al., Journal of Clinical Oncology.
Dosing Schedule For Adjuvant Chemo In High-Risk Early Breast Cancer Can Be Patient's Choice
Patients with high-risk early breast cancer have similar survival outcomes with different dosing schedules of adjuvant anthracycline- and taxane-based chemotherapy, according to research presented at the San Antonio Breast Cancer Symposium 2024.
Dosing decisions should therefore be based on patient preference and differences in the risk of toxicity, according to study presenter Azka Ali, MD, of the Cleveland Clinic Taussig Cancer Institute in Ohio.
Dr Ali and colleagues evaluated different dosing schedules for adjuvant chemotherapy in the phase 3 S0221 trial (NCT00070564), which included 2716 patients with high-risk, stage I-III breast cancer. Patients were originally assigned to receive chemotherapy at 1 of 4 dosing schedules:
At the first interim analysis, the researchers found that weekly doxorubicin and cyclophosphamide was unlikely to be superior to dosing every 2 weeks. Therefore, accrual was suspended, and the trial was later reopened with a revised protocol.
A total of 578 patients were treated under the revised protocol, and they were randomly assigned to 1 of 2 dosing schedules:
Dr Ali noted that there were a few significant differences between patients treated under the original protocol and those treated under the revised protocol. The revised protocol group was older (median age, 53 years vs 51 years; P <.0001), more likely to be node negative (38% vs 23%; P <.0001), and less likely to have hormone receptor (HR)-positive/HER2-negative disease (49% vs 56%; P =.0004).
At 10 years, there were no significant differences in disease-free survival (DFS) or overall survival (OS) across the original 4 study arms. The 10-year DFS rate was 73.3% in arm 1, 69.9% in arm 2, 69.4% in arm 3, and 72.6% in arm 4 (P =.90). The 10-year OS rates were 79.1%, 76.0%, 75.7%, and 78.3%, respectively (P =.34).
Likewise, there were no significant differences in DFS and OS among patients treated under the revised protocol. The 10-year DFS rate was 71.9% in arm 5 and 76.8% in arm 6 (P =.32). The 10-year OS rates were 79.1% and 83.8%, respectively (P =.42).
Subgroup analyses showed that men had worse DFS and OS outcomes than women, Black patients had worse DFS and OS than non-Black patients, and patients with HER2-positive tumors had better DFS and OS than patients with HR-positive/HER2-negative breast cancer or triple-negative breast cancer. Dr Ali noted, however, that it is not clear whether the superior outcomes seen in the HER2-positive group were attributable to chemotherapy or to HER2-directed treatment, as patients were allowed to receive trastuzumab.
Rates of grade 3 or higher cardiotoxicity were similar across the treatment arms, but there were differences in other grade 3 or higher adverse events. Patients treated under the revised protocol had lower rates of cytopenias, there was more hand-foot syndrome among patients who received weekly doxorubicin and cyclophosphamide, and neuropathy was more common among patients who received paclitaxel every 2 weeks for 6 cycles. Details can be seen in the table below.
Grade 3 or Higher Adverse Events Across Arms Arm 1 Arm 2 Arm 3 Arm 4 Arm 5 Arm 6 Neutropenia 25.6% 22.5% 26.4% 24.2% 2.0% 6.7% Anemia 9.0% 5.3% 10.5% 5.5% 3.2% 2.2% Thrombocytopenia 2.5% 3.0% 2.8% 3.0% 0.4% 0% Cardiac Events 3.2% 0.6% 3.0% 0.5% 1.2% 2.2% Hand-Foot Syndrome 2.1% 13.7% 1.5% 14.4% 1.2% 0.7% Neuropathy 15.3% 15.2% 10.5% 8.7% 19.0% 10.5%Based on these results, Dr Ali concluded that the "selection and schedule of regimens should depend on patient preference and toxicity potential."
Disclosures: This research was supported by Amgen and the National Cancer Institute. Dr Ali disclosed relationships with AstraZeneca, Gilead, Guardant, Amplify Health, MJH, OncLive, Curio, and Symbiosis. No other disclosures were provided.
This article originally appeared on Cancer Therapy Advisor
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