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Overall Survival with Fulvestrant and Palbociclib in Advanced HR-Positive, HER2-Negative Breast Cancer
Although the PALOMA-3 trial previously demonstrated that adding the cyclin dependent kinase (CDK) 4/6inhibitor palbociclib to fulvestrant as second-line therapy improved progression-free survival (PFS) in patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, the effect on overall survival (OS) was unknown. In longer-term follow-up, palbociclib improved OS by approximately seven months, but the difference did not achieve statistical significance. The analysis was performed prior to data maturity, and some patients assigned to placebo received a CDK 4/6 inhibitor upon progression. Given prior data, and limitations with the present analysis, we continue to offer the combination of palbociclib plus fulvestrant as second-line therapy for women with metastatic HR-positive, HER2-negative breast cancer.
Hydrochlorothiazide and Risk of Cutaneous Squamous Cell Carcinoma
Previous studies found modest increases in risk for cutaneous squamous cell carcinoma (SCC) among patients using photosensitizing medications, and in particular, thiazide diuretics. A Danish case-control study including over 8,000 patients with SCC and 172,000 controls found that, compared with nonusers, high users of hydrochlorothiazide had a two- to seven-fold increased risk of cutaneous SCC, with a clear dose-response effect. Although additional studies controlling for known risk factors for SCC (eg, sun exposure, phototype, smoking) are still needed, education on sun avoidance and sun protection may be appropriate for patients taking thiazide diuretics.
Updated Clinical Practice Guidelines for Metastatic Pancreatic Cancer
The American Society of Clinical Oncology has published updated clinical practice guidelines for metastatic pancreatic cancer after initial chemotherapy. They support use of an irinotecan plus fluorouracil-based regimen for second-line therapy in patients who retain a good performance status and favorable comorbidity after first-line treatment with gemcitabine plus nabpaclitaxel. Routine testing of the tumor for microsatellite instability/deficient mismatch repair is recommended for patients who would be candidates for checkpoint inhibitor immunotherapy. Our recommendations are consistent with these revised guidelines.
FDG-PET for Residual Masses After Chemotherapy for Metastatic Seminoma
It has been standard practice to perform fluorodeoxyglucose positron emission tomography (FDG-PET) to evaluate residual masses ≥3 cm after chemotherapy for metastatic seminoma, and to pursue resection for FDG-avid masses. The value of FDG-PET for surgical decision making was called into question in a study of 90 men without elevated tumor markers or nonseminomatous histology who had PET-positive residual lesions after chemotherapy for advanced seminoma. Among the 26 who underwent resection, active seminoma was identified in only five (19 percent); the remainder had necrosis and the positive predictive value of FDG-PET was only 23 percent. In our view, further validation of these findings is necessary before a change in practice can be recommended.
Minimally Invasive Approaches to Radical Hysterectomy for Cervical Cancer Associated With Decreased Survival
Minimally invasive surgical approaches (MIS; laparoscopy and robotic surgery) have been utilized for radical hysterectomy in women with cervical cancer, with the goal of reducing operative morbidity. However, two new studies found worse oncologic outcomes with MIS procedures. In a randomized trial of women with cervical cancer who underwent radical hysterectomy, MIS compared with laparotomy resulted in a higher rate of death from cervical cancer at 3 years (4.4 versus 0.6 percent) and a lower rate of disease-free survival at 4.5 years (86.0 versus 96.5 percent). Similarly, a cohort study found that MIS radical hysterectomy was associated with a higher four-year mortality rate (9.1 versus 5.3 percent). Both studies were underpowered to detect a difference in outcomes for tumors <2 cm, which is a significant prognostic factor. MIS results in decreased operative morbidity compared with laparotomy and has been adopted for many abdominal procedures, including oncologic surgery. Since the early 2000s, radical hysterectomy for cervical cancer has been performed using conventional laparoscopy and robotic-assisted laparoscopy, but based on new findings of increased risks of recurrence and mortality compared with laparotomy, we now recommend that radical hysterectomy should be performed via laparotomy for most women with cervical cancer. Further study is needed to explore the safety of MIS approaches in women with the lowest-risk disease.
Sirolimus for Prevention of Skin Cancer in Kidney Transplant Recipients
Solid organ transplant recipients are at increased risk for cutaneous squamous cell carcinomas (SCCs). Previous short-term trials suggest that immunosuppression regimens that include mammalian (mechanistic) target of rapamycin (mTOR) inhibitors, rather than calcineurin inhibitors (CNIs), may reduce the risk of SCC. In a randomized five-year extension trial in kidney transplant recipients on CNI-based immunosuppression who had at least one cutaneous SCC, those assigned to switch to the mTOR inhibitor sirolimus versus continuing CNIs had fewer new skin cancers over five years, with no difference in rejection or mortality. Although we do not routinely use mTOR inhibitors as part of an initial maintenance immunosuppression regimen in kidney transplant recipients, conversion to an mTOR inhibitor is an option for patients taking a CNI who develop a new cancer, including cutaneous SCC, after transplantation.
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