NEWS & PERSPECTIVE
Immunotherapy eliminates tumor cells in early-stage triple-negative breast cancer (KEYNOTE-522 study)
Triple-negative breast cancer (TNBC) is an aggressive form of the disease accounting for 10-20% of all breast carcinomas and characterized by the low expression of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2.1 TNBC represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents, limiting treatment options to chemotherapy. According to the recent findings from KEYNOTE-522 trial presented at the ESMO Congress 2019 in Barcelona, Spain, the addition of immune therapy to chemotherapy improves the pathological complete response (pCR) in patients with early TNBC, giving the emergence of new therapeutic targets for patients with TNBC.2
TNBC is the most aggressive subtype of breast cancer and more often affects young women. Patients typically receive chemotherapy, followed by surgery to remove the tumor, allowing the best chance of pCR. Women with a pCR have a 85–90% likelihood of being cured, while those with residual viable tumor tissue have a 40–50% probability of recurrence, which often occurs within three years.3
KEYNOTE-522, a randomized, placebo-controlled, phase 3 trial of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with early-stage high-risk TNBC, tested whether adding immune therapy to chemotherapy prior to surgery could improve pCR and event-free survival. A total of 1,174 patients were randomized at a 2:1 ratio to pembrolizumab or placebo, both added to preoperative chemotherapy with anthracyclines, taxanes and platinum, for five to six months. After surgery, patients continued their allocated treatment of pembrolizumab or placebo for nine cycles.2
By the time of data presentation at the ESMO Congress 2019, a median follow-up time consisted of 15.5 months. The pCR, assessed in the first 602 patients, significantly increased from 51.2% (95% CI: 44.1-58.3) in the placebo group to 64.8% (95% CI: 59.9-69.5) in the pembrolizumab group (p=0.00055). “We found a 13.6% difference which is a clinically meaningful benefit,” said study author Prof. Peter Schmid, Barts Cancer Institute, Queen Mary University of London, UK.
The interim analysis of event-free survival demonstrated a favorable trend for the pembrolizumab group with a HR of 0.63 (95% CI: 0.43–0.93). This preliminary data provides a strong sign that the addition of immune therapy to neoadjuvant chemotherapy prevents breast cancer recurrence, however, longer time of follow-up is required to confirm these findings.
Treatment-related side effects of grade 3 or higher occurred in 78.0% and 73.0% of the pembrolizumab and placebo groups, respectively. Many of the side effects were driven by the intensive chemotherapy regimen. Side effects with a potential link to immune therapy occurred in 42% of patients in the pembrolizumab group compared with 21% on placebo. “Immune therapy added some side effects to chemotherapy, but there were no new safety signals,” added Prof. Schmid.
While a large benefit in response rate was expected, the poor predictive value of PD-L1 was surprising. “This is probably because most early-stage TNBCs express some degree of PD-L1, sometimes below the predefined cut-off of positivity. The role of chemotherapy as a sensitizer for anti-PD-1 in PD-L1-low early-stage TNBC should also be explored,” commented Prof. Fabrice André, Institut Gustave Roussy, Villejuif, France.“ The next step will be to define which patients are resistant and prioritize which targets should be hit in this population. We also have to determine the impact of this new class of drug on survivorship issues.”
- Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res. 2018;8(5):1483-1507.
- P. Schmid et al. KEYNOTE-522: Phase 3 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early triple-negative breast cancer. Annals of Oncology. Volume 30, Supplement 5, October 2019. https://oncologypro.esmo.org/Meeting-Resources/ESMO-2019-Congress/KEYNOTE-522-Phase-3-study-of-pembrolizumab-pembro-chemotherapy-chemo-vs-placebo-pbo-chemo-as-neoadjuvant-treatment-followed-by-pembro-vs-pbo-as-adjuvant-treatment-for-early-triple-negative-breast-cancer-TNBC. Accessed November 4, 2019.
- Immune Therapy Eliminates Tumour Cells in Early Triple Negative Breast Cancer [ESMO 2019 Press Release]. https://www.esmo.org/Press-Office/Press-Releases/ESMO-Congress-TNBC-breast-cancer-immunotherapy-Keynote522-Schmid. Accessed November 4, 2019.
Future pillar of BCC treatment: Immunotherapy
The incidence of nonmelanoma skin cancer is on the rise in both men and women.1 The treatment of basal cell carcinoma (BCC) can be characterized into 4 major groups, namely surgical (e.g., standard excision, Mohs surgery), destructive (e.g., cryotherapy, lasers), topical (e.g., 5-fluorouracil, imiqu
Results of DESTINY-Breast04: Trastuzumab deruxtecan vs. TPC for HER2-low unresectable and/or mBC
Glossary: BICR: Blinded independent central review; CI: Confidence interval; ECOG: Eastern Cooperation Oncology Group; HER2-: Human epidermal growth factor receptor 2-negative; HR: Hazard ratio; HR+: Hormone receptor-positive; HR-: Hormone receptor-negative; IHC: Immunohistochemistry; ISH: In situ
MAINTAIN: ET with or without ribociclibafter progression on AET + CDK4/6i in patients with unresectable or HR+, HER2- mBC
Glossary: AEs: Adverse events; AI: Aromatase inhibitor; CBR: Clinical benefit rate; CDK4/6i: Cyclin-dependent kinase 4/6 inhibitor; CI: Confidence interval; CR: Complete response; ECOG: Eastern Cooperation Oncology Group; ER+: Estrogen receptor-positive; ET: Endocrine therapy; GnRH: Gonadotropin-r
MONALEESA-2: Impact of ribociclib dose modifications on OS in HR+/HER2- ABC patients
Glossary: 1L: First-line; ABC: Advanced breast cancer; AE: Adverse event; CBR: Clinical benefit rate; CI: Confidence interval; CKD4/6i: Cyclin-dependent kinase 4/6 inhibotor; HER2-: Human epidermal growth factor receptor 2-negative; HR: Hazard ratio; HR+: Hormone receptor-positive; NR: Not reached
Ribociclib plus fulvestratnt has the longest mOS OF over 67 months in postmenopausal breast cancer patients
Cancer is a leading cause of death globally, claiming almost 10 million deaths in 2020.1 Breast cancer is one of the most common cancers in women, with nearly 2.3 million new breast cancer diagnoses in 2020 worldwide.1 Gene-expression profiling has identified distinct subtypes of cancer, among which there are subpopulations expressing specific markers.2 According to the National Institutes of Health (NIH), hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) is the most prevalent breast cancer.3 Cyclin-dependent kinase 4 and 6 (CDK4/6) are good drug targets for cancer, owing to their role in cell cycle progression.4 Ribociclib is one of the 3 inhibitors of CDK4/6 approved in combination with fulvestrant for treating HR+/HER2- advanced breast cancers in adults, based on a series of phase 3 clinical trials called MONALEESA, which tested ribociclib along with different drug partners in HR+/HER2- cancer patients.4-7 The MONALEESA-2 study showed that progression-free survival (PFS) was significantly longer with first-line ribociclib + letrozole than with placebo + letrozole.7 The MONALEESA-7 trial also showed significantly longer median overall survival (mOS) in ribociclib in combination with the endocrine therapy (ET) vs. the placebo arm in postmenopausal HR+/HER2- cancer patients.6 Similarly, the primary MONALEESA-3 trial and its subsequent analysis Demonstrated that ribociclib + fulvestrant had significant OS benefit as compared with placebo in HR+/HER2- patients advanced breast cancer patients.5,6 In a recently held European Society of Medical Oncology (ESMO) Breast Cancer Congress, Neven, et al. presented an updated exploratory mOS analysis result with the longest follow-up of the MONALEESA 3 study to date.8
Optimal breast cancer screening approaches for women with ATM, CHEK2, and PALB2 PVs
Recently, a group of non-BRCA1/2, moderate- to high-risk breast cancer susceptibility genes, have been observed. Among them, the most prevalent ones are ATM, CHEK2 and PALB2.1-3 These pathogenic variants (PVs) can increase the risk of breast cancer by at least 2-fold, thus indicating an obvious and urgent need for screening them.1,3 However, optimal strategies for screening in women carrying these PVs have yet to be well established.1 In a recent study published in the Journal of the American Medical Association (JAMA), Lowry K P and his colleagues conducted a comparative simulation modeling analysis to determine whether screening using mammography and magnetic resonance imaging (MRI) could benefit breast cancer patients with ATM, CHEK2 and PALB2 PVs at various age intervals, which may increase the survival rate in these female patients.1
Poorer survival outcomes in breast cancer patients with chronic stress
The allostatic load, which results from lifelong exposure to social and environmental stressors such as discrimination and poverty, provides with us a way to evaluate the eftects of chronic stress on a patient's physiology.1 Chronic stress has been shown to be associated with various health problems, including hypertension, kidney disease, inflammation, and other conditions.1 According to a recent ECOG-ACRIN E5103 phase 3 clinical trial, Dr. Samilia Obeng-Gysai, a surgical oncologist at The Ohio State University Comprehensive Cancer Center, analyzed the data from the trial on the relationship between allostatic load and clinical outcomes in breast cancer patients, the elevated allostatic load was found to be linked with a lover likelihood of chemotherapy completion and a higher risk of death among breast cancer patients.1
Overcoming the clinical challenges of breast cancer management: From identifying prognostic factors to achieving personalized treatment
Breast cancer is the most common cancer among females in Hong Kong and accounted for 27.2% and 12.4% of all cancer incidences and deaths in 2018, respectively.1 Over the past decade, the incidence and death rate of breast cancer continued to increase while the challenges of managing the disease rema
Advances in the treatment and diagnosis for MPM and thymoma
Malignant pleural mesothelioma (MPM) and thymoma are rare tumor types with limited treatment options.1,2 Chemotherapy regimens with platinum agents plus folate antimetabolites were the only approved first-line MPM treatment from 2004 until last year.1 New treatments and diagnosis are anticipated to foster survival benefit for MPM and thymoma patients.3 More innovative diagnostic and therapeutic techniques for MPM and thymoma were discussed by thoracic oncological experts at the virtual event of World Conference on Lung Cancer 2021.3