Diagnosing and Treating Adult Cancers and Associated Impairments (2021) / Chapter Skim
Currently Skimming:
8 New and Emerging Therapies
8 New and Emerging Therapies
Pages 219-252
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From page 219... ...
The standards of cancer care, which are described in detail in other chapters of this report, can change and evolve rapidly in response to the latest research findings from clinical trials and other research. In this chapter the committee presents an overview of selected new or emerging cancer therapies, which are defined as follows: A new treatment is a therapeutic approach adopted recently in clinical practice or an established treatment for one type of cancer that is being studied for other cancers.
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From page 220... ...
This is followed by a discussion of new and emerging therapies that are organized into three broad categories -- surgery, radiation therapy, and systemic therapies -- and whose use is described for the treatment of lung cancer and breast cancer in particular, but in some cases, other types of cancer as well. The final section of the chapter describes neoadjuvant and multimodal treatment approaches to treating cancer.
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From page 221... ...
These new designs help to reduce the time needed to perform the necessary clinical trials and to make effective drugs available more quickly. SURGERY Although surgical treatment for breast cancer is relatively effective and in the majority of cases results in excision of the tumor such that there are negative margins (i.e., no evidence of cancer)
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From page 222... ...
is removed, along with additional sentinel lymph nodes, which are the first few lymph nodes that drain a breast cancer and are located primarily in the axilla. Sentinel lymph node dissection is not used as a standard approach for patients with clinically node-positive disease (false negative rate is >14% in the European SENTINA trial; Kuehn et al., 2013)
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From page 223... ...
Finally, these techniques have been applied for malignancies other than breast cancer that are treated with lymph node dissection, such as melanomas and head and neck cancers. Axillary Reverse Mapping The goal of axillary reverse mapping is to avoid the removal of the lymph nodes that drain an arm during lymph node surgery for breast cancer and thereby preserve lymphatic flow from that extremity (Thompson et al., 2007)
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. A multi-institutional randomized phase III clinical trial is now under way to study how effective axillary reverse mapping is in preventing lymphedema in breast cancer patients undergoing ALND (Alliance for Clinical Trials in Oncology, 2019)
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Multiple studies have since confirmed the oncologic safety of laparoscopic surgery, and this approach is now commonly performed and considered standard of care for some solid tumors (e.g., colorectal, kidney, and prostate cancers) (Cohen and Kingham, 2019)
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Breast cancer patients with triple-negative or HER2-amplified tumors who have a complete response after neoadjuvant chemotherapy ("exceptional responders") may be eligible for clinical trials to determine whether surgery can be omitted (Kuerer et al., 2018; van der Noordaa et al., 2018)
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From page 227... ...
Thus, compared with photon therapy, proton therapy and carbon ion therapy have the advantage of protecting adjacent organs or soft tissues from receiving radiation, which could lead to fewer short-term and long-term effects. Although they have been in existence for several decades, the cost of these charged-particle therapies limits their use.
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From page 228... ...
. There has been much less clinical experience with carbon ion radiotherapy than with proton radiation therapy, and, as such, investigators from the National Institute of Radiological Sciences in Japan concluded that randomized clinical trials are needed to determine if carbon ion radiotherapy is superior to photon or proton radiotherapy (Kamada et al., 2015)
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From page 229... ...
. Randomized phase III clinical trials have demonstrated a clinical benefit of PARP inhibitors in tumors associated with germline mutations in BRCA1 and BRCA2.
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A recent phase II study found that olaparib was effective for patients with metastatic breast cancer who had germline PALB2 mutations or somatic BRCA1/2 mutations, expanding the population of patients with breast cancer who might benefit from PARP inhibitors beyond germline BRCA1/2 mutation carriers (Tung et al., 2020)
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From page 231... ...
Mutations in EGFR are now known to drive the growth a number of cancers, particularly lung cancer, where EGFR mutations are present in approximately 10% of all advanced non-small-cell lung cancer (NSCLC) patients and in about 40% of patients who are never-smokers (Pao et al., 2004)
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. A major advance in lung cancer research has been the discovery of a common resistance mechanism to these first-generation agents.
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From page 233... ...
The availability of all these oral inhibitors means that patients can be treated for a number of years sequentially with targeted agents before traditional systemic chemotherapy is used. A recent study demonstrated the superiority of ALK inhibitors over chemotherapy for metastatic NSCLC, with more than 50% of patients receiving ALK inhibitors alive at 6.8 years, compared with only 2% of those receiving chemotherapy alive at 5 years (Pacheco et al., 2019)
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. Other Targeted Therapies As noted in Chapter 4, targeted therapies can act in a number of ways, including preventing the proliferation of mutant proteins in cancer cells and identifying chromosome aberrations that produce fusion genes and thus fusion proteins.
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From page 235... ...
Immunotherapy As discussed in Chapter 4, immunotherapy harnesses the body's own immune system to recognize cancer cells as foreign and release chemicals called cytokines which kill these cancer cells. Cancer immunotherapy can be broadly classified into the following categories: cancer vaccines, adoptive cellular therapy, and immune checkpoint inhibitors.
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From page 236... ...
There are a large number of therapeutic vaccines in clinical trials, and it is likely that a number of these candidate vaccine therapies will be approved for cancer treatment in the coming years. Adoptive Cellular Therapies In this type of immunotherapy, T cells, a type of immune cell that fights cancer, are removed from the patients' body, grown in very large numbers in the laboratory, and then infused back into the patient to assist the immune system in killing cancer cells.
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From page 237... ...
For patients whose cancers recur after an autologous hematopoietic stem cell transplant or for those patients whose cancer no longer responds to traditional chemotherapies, CAR T-cell therapy offers potential long-term disease control. Its use as a treatment for solid tumors is being explored in clinical trials.
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From page 238... ...
When this protein is blocked, the "brakes" on the immune system are released, and the ability of T cells to kill cancer cells is increased. Immune checkpoint inhibitors have emerged as an increasingly important cancer treatment.
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From page 239... ...
PD-1 Inhibitors Cemiplimab Squamous cell skin cancer Nivolumab Melanoma, non-small-cell lung cancer, small-cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, microsatellite instability-high colorectal cancer, hepatocellular carcinoma Pembrolizumab Melanoma, non-small-cell lung cancer, small-cell lung cancer, head and neck squamous cell carcinoma, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high cancers, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial carcinoma, metastatic breast cancer PD-LI Inhibitors Atezolizumab Urothelial carcinoma, non-small-cell lung cancer, triple-negative breast cancer, small-cell lung cancer Avelumab Merkel cell carcinoma, urothelial carcinoma; renal cell carcinoma (in combination with axitinib) Durvalumab Urothelial carcinoma, non-small-cell lung cancer, small-cell lung cancer SOURCE: Information from Vaddepally et al., 2020.
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From page 240... ...
. LONG-TERM OUTCOMES OF NEW AND EMERGING THERAPIES There is a wide array of new and emerging treatment approaches for cancer described in this chapter.
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From page 241... ...
These limitations mean that there will be gaps in knowledge about what to expect in terms of both short- and long-term toxicity and how these may affect the patient's ability to work and carry out usual activities. In contrast, some of the emerging treatment approaches in surgery and radiation therapy may provide benefit in terms of reducing treatmentassociated morbidities and thus allow for improved function and survival after treatment.
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From page 242... ...
Immunotherapy for cancer can take the form of preventive vaccines such as human papilloma virus and hepatitis B, both of which are associated with several cancers; therapeutic vaccines that activate the immune re sponse against a patient's tumor; adoptive cellular therapies such as chimeric antigen receptor T-cell therapy; and immune checkpoint inhibitors such as programmed cell death protein-1. Conclusions 1.
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From page 243... ...
2019. Axillary reverse mapping in preventing lymph edema in patients with breast cancer undergoing axillary lymph node dissection.
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From page 244... ...
2016. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3)
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From page 245... ...
2015. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treat ment in breast cancer patients: The MARI procedure.
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From page 246... ...
2015. Carbon ion radiotherapy in Japan: An assessment of 20 years of clinical experience.
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2017. Broadening eligibility criteria to make clinical trials more repre sentative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement.
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2015. Is axillary reverse mapping feasible in breast cancer patients?
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2012. Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer.
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2018. Identifying pathologic complete response of the breast after neoadjuvant systemic therapy with ultrasound guided biopsy to eventually omit surgery: Study design and feasibility of the MICRA trial (Minimally Invasive Complete Response Assessment)
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2012. Trastu zumab emtansine for HER2-positive advanced breast cancer.
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