Antibody-Drug Conjugates in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer. It is a heterogeneous breast cancer subtype with a poor prognosis. Given these negative features, there is a need for new treatment options beyond conventional chemotherapy in both the early stage and palliative setting. Impressive results have been reported with antibody-drug conjugates (ADCs) that link a cytotoxic payload to a monoclonal antibody, such as sacituzumab govitecan and trastuzumab deruxtecan, in the metastatic stage. The focus of this review is to discuss completed and ongoing trials involving ADCs in TNBC.

Trop-2 as a Therapeutic Target in Breast Cancer.

The emergence of Trop-2 as a therapeutic target has given rise to new treatment paradigms for the treatment of patients with advanced and metastatic breast cancer. Trop-2 is most highly expressed in triple negative breast cancer (TNBC), but the receptor is found across all breast cancer subtypes. With sacituzumab govitecan, the first FDA-approved, Trop-2 inhibitor, providing a survival benefit in patients with both metastatic TNBC and hormone receptor positive breast cancer, additional Trop-2 directed therapies are under investigation. Ongoing studies of combination regimens with immunotherapy, PARP inhibitors, and other targeted agents aim to further harness the effect of Trop-2 inhibition. Current investigations are also underway in the neoadjuvant and adjuvant setting to evaluate the therapeutic benefit of Trop-2 inhibition in patients with early stage disease. This review highlights the significant impact the discovery Trop-2 has had on our patients with heavily pretreated breast cancer, for whom few treatment options exist, and the future direction of novel Trop-2 targeted therapies.

When the World Throws You a Curve Ball: Lessons Learned in Breast Cancer Management.

In the care of patients with operable breast cancer, there has been a shift toward increasing use of neoadjuvant therapy. There are benefits to neoadjuvant therapy, such as monitoring for response, as well as an increased rate of breast conservation and reduction of potential morbidity associated with breast surgery, including axillary management. Among patients with highly proliferative tumors, such as HER2-positive or triple-negative breast cancer, those with residual disease are at higher risk of recurrence, which informs the recommended systemic therapy in the adjuvant setting. For instance, in patients with residual disease after neoadjuvant chemotherapy and HER2-targeted therapy, there is a role for adjuvant trastuzumab emtansine for those with residual disease at the time of surgery. The same holds true regarding the role of adjuvant capecitabine in patients with residual disease after neoadjuvant chemotherapy. With the added complexities of treating patients in the era of the COVID-19 outbreak, additional considerations are critical, including initiation of surgery within an appropriate time from completion of neoadjuvant therapy. National consensus guidelines on time to surgery must be developed to improve measurement and comparison across systems. In addition, there is emerging radiation treatment management research addressing a number of factors, including hypofractionation, role of proton beam therapy, safe omission of radiotherapy, and preoperative radiotherapy with or without drug combination. In this article, the multidisciplinary approach of treating patients with operable breast cancer is highlighted, with updates and future considerations described.

Outcomes of patients with oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiation compared with those treated with concurrent chemoradiation.

BACKGROUND: Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established. METHODS: The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence. RESULTS: In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS. CONCLUSIONS: In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings.

Subjective functional outcomes in oropharyngeal cancer treated with induction chemotherapy using the MD Anderson Symptom Inventory (MDASI).

OBJECTIVES: Evaluate the use of induction chemotherapy (IC) in oropharyngeal cancer (OPC) and its impact on subjective functional outcomes using a validated MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) survey tool. METHODS: A single institution retrospective review of OPC patients who received IC, including reasons given for using IC, regimens employed, responses, and patient-reported outcomes (PRO). The latter included pain, distress, dysphagia, xerostomia, and feeding tube placement and dependency. PRO's were assessed using the validated MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) conducted at baseline, during treatment, and at six-month follow up. RESULTS: One hundred and twenty-five patients were evaluable. They were more likely to have large primary and/or bulky or low neck nodal disease as a reason for IC. A taxane-containing regimen was most common. Primary tumor response was seen in 83.2% and the nodal response in 81.6%. Pain and xerostomia improved with IC, dysphagia was not adversely affected with IC. These symptoms all increased with consolidation chemoradiotherapy (CRT) but returned to baseline by 6 months post treatment. Feeding tube placement did not increase with IC but did with CRT, most patients were no longer feeding tube dependent at 6 months. CONCLUSION: This retrospective review of subjective functional outcomes, especially swallowing and feeding tube dependency, using the MDASI survey tool in 125 oropharyngeal cancer patients with large primary tumors and/or bulky adenopathy treated predominantly with platinum-taxane based induction chemotherapy showed that such outcomes were not adversely impacted. While not standard, such approach may be beneficial in such patients. LEVEL OF EVIDENCE: 2.

Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear. METHODS: 1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3). RESULTS: 7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18-25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.21) and Group 3 (HPV-/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.012) and Group 3 (HPV-/unknown) (p = 0.002). CONCLUSIONS: There was no observed difference in the time to development of DM between the HPV-/unknown and HPV+ HNSCC groups. However, the HPV+ HNSCC group showed a higher rate of DM to the lung compared to the HPV-/unknown -HNSCC group (p = 0.002).