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Neoadjuvant T-DM1 in HER2-positive breast cancer (September 2021)

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that has demonstrated impressive single-agent activity in patients with HER2-positive metastatic breast cancer, but its role in early breast cancer is less clear. In a randomized trial, which included women with HER2-positive breast cancers 2 cm, neoadjuvant single-agent T-DM1 resulted in a similar pathologic complete response rate as docetaxel, trastuzumab, and pertuzumab (44 versus 46 percent) [1]. However, other data have suggested a higher rate of locoregional progression with T-DM1 relative to a standard neoadjuvant chemotherapy regimen that incorporates anti-HER2 antibody therapy. Therefore, pending further data, we do not consider T-DM1 to be a standard neoadjuvant regimen in HER2-positive breast cancer.

Tebentafusp for metastatic uveal melanoma (April 2021, Modified September 2021)

Metastatic uveal melanoma is a rare, aggressive malignancy with few effective treatment options. There is interest in developing novel T-cell receptor therapeutics for this disease, such as tebentafusp, which specifically targets glycoprotein 100, a uveal melanoma antigen. In a phase III trial of almost 400 patients with positive human leukocyte antigen-A*0201 and systemic treatment-naive advanced uveal melanoma, tebentafusp improved overall survival (OS) compared with investigator's choice of immunotherapy or chemotherapy (one-year OS 73 versus 59 percent) [2]. These data are promising, and we await regulatory approval of tebentafusp prior to incorporating it into routine clinical practice.

Updated guidelines for cervical cancer screening in patients with HIV (August 2021)

In August 2021, the United States Department of Health and Human Services along with the National Institutes of Health published updated guidelines for the screening of cervical cancer in patients with HIV. In contrast to the previous guideline, cervical cancer screening at the time of HIV diagnosis is now limited to patients age 21 years or older [3]. We also follow these updated guidelines for patients without HIV who are on long-term immunosuppressive therapy (eg, solid organ transplant, allogeneic hematopoietic stem cell transplant, systemic lupus erythematous, and those with inflammatory bowel disease or rheumatologic disease requiring current immunosuppressive treatments).

Ivosidenib approved for advanced IDH1-mutated cholangiocarcinoma (August 2021)

Mutations in one of the isocitrate dehydrogenase (IDH) genes are present in up to 25 percent of advanced cholangiocarcinomas, particularly intrahepatic tumors. The oral IDH1 inhibitor ivosidenib has been approved by the US Food and Drug Administration (FDA) for treatment of adults with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation, as detected by an FDA-approved test [4]. Approval was based on the randomized placebo-controlled Clar1DHy trial, which showed modestly prolonged survival and durable responses with ivosidenib [5]. Although adverse reactions (nausea, vomiting, fatigue) were common, they were mostly low-grade.

Nivolumab plus chemotherapy in advanced NSCLC (August 2021)

Combinations of immunotherapy and chemotherapy are being investigated in treatment-naive advanced non-small cell lung cancer (NSCLC). In a trial in 550 treatment-naive patients with stage IIIB-IV nonsquamous NSCLC, the addition of nivolumab to bevacizumab, carboplatin, and paclitaxel increased progression-free survival (PFS; 12.1 versus 8.1 months) [6]. The PFS benefit was observed irrespective of PD-L1 expression. Although the PFS outcome in the nivolumab group was notable, we await further data or regulatory approval prior to routine use of this regimen.

1. Hatschek T, Foukakis T, Bjohle J, et al. Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021;7(9):1360.

2. Nathan P, Hassel JC, Rutkowski P, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021;385(13):1196.

3. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.p (Accessed on August 19, 2021)

4. US FDA approval letter for ivosidenib in advanced cholangiocarcinoma https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2021/211192Orig1s008ltr (Accessed on August 30, 2021).

5. Zhu AX, Macarulla R, Javle MM, et al. Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation (abstract). J Clin Oncol 39, 2021 (suppl 3; abstr 266).

6. Sugawara S, Lee JS, Kang JH, et al. Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2021;32(9):1137. Epub 2021 Jun 15.

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