Nov 18, 2022
ASCO seeks to advance the education of all oncology professionals and ultimately facilitate and support enhanced patient care. The ASCO Oncology Self-Assessment Series on ASCO Connection consists of free case-based multiple-choice practice questions, educational links, and answer rationales from ASCO-SEP.
Learn more about ASCO’s Educational products, such as the 2022 ASCO-SEP Digital Subscription, which includes the digital book, access to education courses and virtual meeting–related content, plus over 1000 practice questions in the Question Bank. Oncology trainees and Training Program Directors can visit Education Essentials for Oncology Fellows (EEOF) to learn more and register for the 2022-23 cycle.
Correct answers are listed at the bottom of the page.
Question 1: Breast Cancer
A 65-year-old woman presents with a history of stage I breast cancer in her left breast that was estrogen receptor–negative, progesterone receptor–negative, and HER2-positive by immunohistochemistry. Four years ago, she was treated with paclitaxel and trastuzumab in the adjuvant setting. She recently underwent staging scans for worsening back pain, which showed multiple sclerotic lesions on the spine and a 2-cm enhancing lesion in the liver. A core biopsy of the liver mass revealed adenocarcinoma consistent with breast primary that was estrogen receptor–negative, but HER2-positive. The patient has well-controlled type 2 diabetes and is otherwise in good health. MRI of the brain was negative for metastatic lesions.
What is the most appropriate first-line systemic therapy for this patient?
- Trastuzumab emtansine (T-DM1)
- Docetaxel and trastuzumab
- Docetaxel, trastuzumab, and pertuzumab
- Capecitabine, trastuzumab, and tucatinib
Question 2: Gynecologic Cancers
A 67-year-old woman presents with postmenopausal bleeding. An endometrial biopsy shows high-grade carcinoma with serous features. CT imaging of the abdomen and pelvis shows an enlarged uterus with diffuse endometrial thickening and a 6-cm mass with no evidence of disease extension. She undergoes total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, and paraaortic and pelvic lymph node dissection, which reveal that disease is present in the omentum and the pelvic lymph nodes. A tumor analysis shows positive staining for MLH1, PMS2, MSH2, MSH6, and HER2 (3+ on immunohistochemistry). CT imaging of the chest shows no evidence of metastatic disease.
In addition to carboplatin and paclitaxel, which of the following should you recommend now?
- Trastuzumab and bevacizumab
- Bevacizumab and pembrolizumab with interdigitated radiation therapy
Question 1 Rationale and Reference
Correct answer: C. Docetaxel, trastuzumab, and pertuzumab
Rationale: This patient is being treated for metastatic HER2-positive breast cancer in the first-line setting. Based on the CLEOPATRA trial, the addition of pertuzumab to docetaxel and trastuzumab led to a significant overall survival benefit. The docetaxel, trastuzumab, and pertuzumab combination regimen remains the standard of care for first-line treatment of metastatic HER2-positive breast cancer. Single-agent T-DM1 and the combination of tucatinib, trastuzumab, and capecitabine are only approved for treatment of metastatic HER2-positive breast cancer in the later line settings.
- Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-34. DOI: https://doi.org/10.1056/NEJMoa1413513
Question 2 Rationale and References
Correct answer: B. Trastuzumab
Rationale: In a randomized phase 2 study of HER2-overexpressing uterine serous carcinoma (USC), trastuzumab with carboplatin and paclitaxel yielded a progression-free survival (PFS) benefit when compared to chemotherapy alone in advanced-stage disease (median PFS, 17.9 months versus 9.3 months), as well as recurrent disease (9.2 months versus 6.0 months). An updated survival analysis demonstrated that overall survival was significantly higher in the trastuzumab with chemotherapy arm compared to the control arm, with medians of 29.6 months versus 24.4 months. In the subset of patients with stage III to IV disease, the survival median was not reached in the trastuzumab-containing arm versus 24.4 months in the control arm. Based on this trial, the NCCN guidelines incorporated the recommendation that carboplatin, paclitaxel, and trastuzumab are the preferred regimen for HER2-positive advanced or platinum-sensitive recurrent USC. Retrospective analyses of the National Cancer Database, as well as data from SEER, demonstrated benefit from chemotherapy with radiation therapy compared to chemotherapy alone in stage III to IV USC, significant only in women receiving chemotherapy before radiation; however, this regimen does not include trastuzumab and the latter is favored in this population. Bevacizumab and pembrolizumab are not approved in this setting.
- Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018;36(20):2044-51. DOI: https://doi.org/10.1200/JCO.2017.76.5966
- Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress Her2/neu (NCT01367002): updated overall survival analysis. Clin Cancer Res. 2020;26(15):3928-35. DOI: https://doi.org/10.1158/1078-0432.CCR-20-0953
- Mahdi H, Nutter B, Abdul-Karim F, Amarnath S, Rose PG. The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone. J Gynecol Oncol. 2016;27(2):e19. DOI: https://doi.org/10.3802/jgo.2016.27.e19
- Lester-Coll NH, Park HS, Rutter CE, et al. Who benefits from chemoradiation in stage III-IVA endometrial cancer? An analysis of the National Cancer Data Base. Gynecol Oncol. 2016;142(1):54-61. DOI: https://doi.org/10.1016/j.ygyno.2016.04.544