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Sacituzumab govitecan in metastatic triple negative breast cancer (May 2021)

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2, a protein overexpressed in the majority of triple negative breast cancers (TNBCs), for the selective delivery of SN-38, the active metabolite of irinotecan. In a randomized trial that enrolled 468 patients with metastatic triple-negative breast cancer that was relapsed or refractory to two or more previous standard chemotherapy regimens, sacituzumab govitecan improved overall survival compared with clinician's choice of chemotherapy (12.1 versus 6.7 months) [1]. Grade >=3 treatment-related neutropenia and diarrhea were more frequent with sacituzumab govitecan. This agent is approved by the US Food and Drug Administration for adult patients with unresectable locally advanced or metastatic TNBC who have received at least two prior therapies, at least one of them for metastatic disease [2].


Immunotherapy combination approved for initial treatment of advanced gastric cancer (April 2021)

Nivolumab has been approved in combination with a fluoropyrimidine and platinum-containing regimen for initial treatment of advanced/metastatic gastric, gastroesophageal junction (EGJ) and esophageal adenocarcinoma, irrespective of PD-L1 expression. Approval was based on a preliminary report of a trial in which over 1500 patients with previously untreated, HER2-negative advanced metastatic gastric, EGJ, or esophageal adenocarcinoma were randomized to nivolumab plus chemotherapy or chemotherapy alone [3]. Nivolumab improved median progression-free and overall survival, and benefits were most pronounced if PD-L1 was highly expressed (median survival 18 versus 9 months for combined positive score [CPS] >=5). In a later analysis, nivolumab modestly improved median survival when all CPS groups were pooled, but not for subgroups with CPS <5 [4]. Although the FDA approval was broad, in our view, the benefits of immunotherapy for adenocarcinomas with low-level or no expression of PD-L1 (ie, CPS <5) remain uncertain, and we suggest initial chemotherapy rather than immunotherapy in these patients, unless they have mismatch repair-deficient tumors.


Lack of survival benefit for atezolizumab in advanced urothelial carcinoma (May 2021)

Atezolizumab, a programmed cell death ligand 1 (PD-L1) inhibitor, initially showed efficacy in advanced, platinum-refractory urothelial carcinoma, leading to its accelerated approval by the US Food and Drug Administration (FDA) in 2017. However, in a phase III trial of over 900 patients with metastatic urothelial carcinoma treated with prior platinum-based chemotherapy, atezolizumab did not improve overall survival over chemotherapy [5]. Based on these data, the FDA withdrew regulatory approval for atezolizumab in patients with locally advanced or metastatic urothelial carcinoma who have progressed on platinum-based chemotherapy [6], and we no longer use it for this indication.


Dostarlimab in dMMR advanced, platinum-refractory endometrial cancer (May 2021)

Immune checkpoint inhibitors have shown particular efficacy among mismatch repair deficient (dMMR) cancers, including endometrial cancer. In a single-arm study including over 70 patients with advanced dMMR endometrial cancer, the objective response rate to the immune checkpoint inhibitor dostarlimab was 42 percent, with 13 percent experiencing a complete response [7]. Anemia, colitis, and diarrhea were the most common grade 3 or higher treatment-related adverse events, but each occurred in <5 percent of patients. These results supported US Food and Drug Administration approval of dostarlimab for patients with advanced or recurrent dMMR endometrial cancer that has progressed on prior platinum based chemotherapy [8], and we consider it a reasonable option in this setting.


1. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529.


2. Sacituzumab govitecan-hziy injection. United States Prescribing Information. US National Library of Medicine. (Accessed on May 11, 2021).


3. Moehler M, Shitara K, Garrido M, et al. LBA6_PR - Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Ann Oncol. 2020;31S:ESMO #S1142.


4. Updated US prescribing information for nivolumab available online at (Accessed on April 19, 2021).


5. Powles T, Duran I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018;391(10122):748. Epub 2017 Dec 18.


6. United States FDA Prescribing Label for Atezolizumab. (Accessed on April 16, 2021).


7. Oaknin A, Tinker AV, Gilbert L, et al. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020;6(11):1766.


8. Dostarlimab-gxly injection. United States Prescribing Information. US National Library of Medicine. (Accessed on April 28, 2021).


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