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Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer (December 2022)
For patients with HER2-positive metastatic breast cancer, antibody-drug conjugates are available after progression on trastuzumab and a taxane, but the optimal sequence has been unclear. In the phase III Destiny-Breast03 trial among 524 patients with HER2-positive metastatic breast cancer with progression on a trastuzumab- and taxane-containing regimen, trastuzumab deruxtecan (T-DXd) improved overall survival compared with trastuzumab emtansine (T-DM1; hazard ratio 0.64).1 Grade >=3 adverse events occurred in 56 percent on T-DXd and 52 percent on T-DM1. Interstitial lung disease occurred in 15 and 3 percent, respectively. Based on results of this trial, for patients with HER2-positive metastatic breast cancer that is progressive on a taxane and trastuzumab, we suggest T-DXd as next-line therapy rather than T-DM1.
Rucaparib maintenance in newly diagnosed ovarian cancer (December 2022)
For newly diagnosed advanced ovarian cancer with response to platinum-based chemotherapy, maintenance with the poly(ADP-ribose) polymerase (PARP) inhibitor niraparib improves progression-free survival (PFS), but trials are evaluating other PARP inhibitors. In a trial in 538 patients with newly diagnosed stage III to IV, high-grade ovarian cancer undergoing surgical cytoreduction and responding to platinum-doublet chemotherapy, rucaparib maintenance improved PFS relative to placebo (20 versus 9.2 months).2 PFS benefits were observed both in homologous repair deficient (HRD) tumors and those lacking HRD, although benefits were lesser in this group. We await regulatory approval prior to using rucaparib maintenance in newly diagnosed ovarian cancer.
Adjuvant nivolumab for high-risk node-negative melanoma (December 2022)
In patients with resected, high-risk node-negative (stage IIB and IIC) cutaneous melanoma, one year of adjuvant pembrolizumab reduces recurrence risk, but studies are evaluating other immune checkpoint inhibitors. In an open-label phase III trial (CheckMate-76K) of almost 800 patients with resected stage IIB and IIC melanoma, one year of adjuvant nivolumab improved one-year recurrence-free survival over placebo (89 versus 79 percent) and was well tolerated.3 Based on these data, for patients with high-risk node-negative (stage IIB and IIC) cutaneous melanoma, we suggest one year of adjuvant immunotherapy with either pembrolizumab or nivolumab.
Lack of benefit of CBD oil for relief of symptoms in advanced cancer (December 2022)
Cannabidiol (CBD) is a naturally occurring molecule without psychoactive properties that can be procured by patients from legal marijuana dispensaries, online companies, or street suppliers. Although CBD oil is used by patients for a variety of conditions, there are few data on the risks and benefits in patients with cancer. A single phase II randomized trial of CBD oil for relief of symptoms in advanced cancer concluded that, compared with placebo, CBD oil did not add value to the reduction in symptom distress (including pain, nausea, vomiting, appetite loss, depression, or anxiety) provided by specialist palliative care.4 Use of CBD oil cannot be recommended for symptom management in advanced cancer.
Chemotherapy for localized Ewing sarcoma (December 2022)
For patients with localized Ewing sarcoma (ES), vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide plus etoposide (VDC/IE) is used in the United States as neoadjuvant therapy, while vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) is used in Europe. In a randomized phase III trial (EE2012) of over 600 patients with ES, initial treatment with VDC/IE improved overall survival over VIDE (three-year overall survival 82 versus 75 percent), reduced rates of grade >=3 febrile neutropenia (58 versus 74 percent), and shortened treatment duration by two months.5 Based on these data, for patients with localized ES, we recommend initial chemotherapy with VDC/IE rather than VIDE.
1. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022;online on 12/7/22.
2. Monk BJ, Parkinson C, Lim MC, et al. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;suppl 17: abstr LBA5500.
3. Long, et al. Adjuvant therapy with nivolumab versus placebo in patients with Stage IIB/C melanoma (CheckMate-76K). Society of Melanoma Research. Presented as a late-breaking plenary abstract on October 19, 2022. https://clin.larvol.com/abstract-detail/SMR%202022/60490438 (Accessed on December 06, 2022).
4. Hardy J, Greer R, Huggett G, et al. Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD). J Clin Oncol. 2022.
5. Brennan B, Kirton L, Marec-Berard P, et al. Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial. Lancet. 2022;400(10362):1513.
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