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Initial dosing of fam-trastuzumab deruxtecan in metastatic HER2-positive colorectal cancer (July 2023)
For patients with HER2-overexpressing metastatic colorectal cancer (mCRC) who progress on trastuzumab-based therapy, fam-trastuzumab deruxtecan (T-DXd) is an effective later-line treatment option, but it can cause significant toxicity, such as interstitial lung disease (ILD). In a randomized phase II trial, every-three-weeks administration of T-DXd at 5.4 mg/kg was similarly effective as 6.4 mg/kg (median progression-free survival 6 versus 5 months) and reduced toxicity, including rates of ILD (8 versus 13 percent).1 Based on these data, for patients with RAS wild-type, HER2-overexpressing mCRC who previously received trastuzumab-based therapy and two or more chemotherapy regimens, we initiate T-DXd at 5.4 mg/kg every three weeks.
Standard versus extended lymphadenectomy for radical cystectomy (August 2023)
The benefit of an extended lymphadenectomy during radical cystectomy is controversial. In a phase III trial, 618 patients with cT2-4a N0-2 bladder cancer underwent radical cystectomy with standard or extended lymphadenectomy and were followed for six years.2 Although more lymph nodes were removed with extended lymphadenectomy (median 39 versus 25), this did not result in more favorable outcomes as rates of nodal metastasis, disease-free survival, and overall survival were similar. Furthermore, extended lymphadenectomy resulted in a higher rate of severe complications (16 versus 8 percent) and more deaths within 90 days (19 versus 7 patients). Given these results, radical cystectomy should be performed with bilateral standard lymphadenectomy, which includes removal of at least 12 external and internal iliac and obturator nodes.
Resection versus biopsy of glioblastoma in older adults (August 2023)
The role of surgical resection in older adults with glioblastoma is controversial. In the first completed trial, 101 older adults (>=70 years) with a suspected operable glioblastoma were randomly assigned to either resection or biopsy, followed by radiation therapy (in all patients) and temozolomide (in later years of the trial).3 Although overall survival was similar between groups (9.4 versus 9.0 months), progression-free survival and quality-of-life outcomes favored resection. The trial was limited by slow enrollment, and confidence intervals for survival were wide. We continue to suggest maximal safe resection for most older adults with operable tumors who are good surgical candidates.
Role of statin therapy in prevention of anthracycline cardiotoxicity (August 2023)
In patients with cancer, studies are evaluating the use of statins to prevent anthracycline-associated heart failure (HF). In a placebo-controlled trial of 300 patients with lymphoma scheduled to receive anthracycline-based therapy, the atorvastatin group had less of a decline in left ventricular ejection fraction (LVEF) at one-year follow-up (4.1 versus 5.4 percent), and fewer patients assigned to atorvastatin had an LVEF decline of >=10 percent to a final LVEF of <55 percent (9 versus 22 percent).4 This study used LVEF as a surrogate endpoint for HF and was not designed to detect differences incident HF or survival. As such, for patients with cancer who will receive anthracyclines, we do not routinely treat with a statin to prevent HF.
Direct oral anticoagulants and cancer-related venous thromboembolism (August 2023)
In patients with cancer-related venous thromboembolism (VTE), accumulating evidence suggests similar safety and efficacy when individual direct oral anticoagulants (DOACS) are compared with subcutaneous low molecular weight heparin (LMWH). In a recent randomized trial of over 670 patients with cancer-related VTE, six-month rates of recurrent VTE (6.1 [DOACs] versus 8.8 percent [LMWH]) and major bleeding (5.2 [DOACs] versus 5.6 percent [LMWH]) were not significantly different.5 Despite limitations (eg, lack of blinding, late randomization, poor adherence rates with LMWH), these data are in keeping with previous evidence and support the administration of DOACs or LMWH as first-line agents in patients with cancer-associated VTE.
1. Singh Raghav KP, Siena S, Takashima A, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): Primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study. J Clin Oncol. 2023;41;16S
2. Lerner SP, Tangen C, Svatek RS, et al. SWOG S1011: A phase III surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at time of radical cystectomy for muscle invasive urothelial cancer. J Clin Oncol. 2023;41:16 suppl.
3. Laigle-Donadey F, Metellus P, Guyotat J, et al. Surgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Francaise (ANOCEF) trial. J Neurosurg. 2023;138(5):1199. Epub 2022 Oct 14.
4. Neilan TG, Quinaglia T, Onoue T, et al. Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial. JAMA. 2023;330(6):528.
5. Schrag D, Uno H, Rosovsky R, et al. Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial. JAMA. 2023;329(22):1924.
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