Natalie S. Callander, MD, a professor of medicine of the the Division of Hematology/Oncology at the University of Wisconsin Carbone Cancer Center, discusses selecting a frontline treatment strategy for patients with multiple myeloma.

When selecting treatment for patients with newly diagnosed multiple myeloma, it’s important to select an approach that produces deep responses with limited adverse effects, Callander says. If a patient is experiencing organ dysfunction related to their disease, reversing the condition should be a priority, Callander adds. Although a patient may appear to be quite ill, it's important to determine whether symptom bother is because of their disease or due to a preexisting condition, which could make them less fit for treatment.

Although determining transplant eligibility is often done upon diagnosis, this is a factor that can change over time as patients demonstrate clinical improvements, Callander explains. For patients who may undergo an autologous stem cell transplant, it's necessary to select a regimen that will not interfere with stem cell collection, adds Callander.

With many agents emerging in the paradigm, the hope is that some of these options will induce deep responses in patients, Callander says. One of the main areas of debate are the questions of whether a triplet or quadruplet should be used in this patient population and whether a doublet regimen still shows benefit in some patients, Callander concludes.

Videos

Natalie S. Callander, MD, discusses selecting a frontline treatment strategy for patients with multiple myeloma.









 Dr. Callander on Selecting a Frontline Treatment Strategy in Multiple Myeloma

Kristen K. Ciombor, MD, MSCI, assistant professor of medicine, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive metastatic gastric cancer. 

 for the treatment of patients with locally advanced or metastatic HER2-positive gastric/gastroesophageal junction (GEJ) cancer who received a prior trastuzumab (Herceptin)-based regimen. The regulatory decision was based on findings from the phase 2 DESTINY-Gastric01 trial in which the antibody-drug conjugate improved overall survival and induced a higher objective response rate compared with chemotherapy in this patient population. 

Trastuzumab deruxtecan is a welcome addition to the gastric/GEJ cancer armamentarium, says Ciombor. However, as some patients will lose HER2 expression, routine biopsies are needed to determine whether the patient expresses the HER2 target and is still eligible to receive trastuzumab deruxtecan, Ciombor concludes. 

Kristen K. Ciombor, MD, MSCI, discusses the FDA approval of fam-trastuzumab deruxtecan-nxki in HER2-positive metastatic gastric cancer.  



Dr. Ciombor on the FDA Approval of Trastuzumab Deruxtecan in HER2+ Metastatic Gastric Cancer 

Joleen M. Hubbard, MD, associate professor of oncology, consultant, practice chair, and vice chair, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses sequencing challenges regarding EGFR inhibitors in colorectal cancer (CRC).

 wild-type CRC, the question of when to sequence EGFR inhibitors remains largely unanswered, Hubbard says. As such, discussing EGFR inhibitors as an option with patients is important. 

Utilizing EGFR inhibitors as maintenance therapy presents additional challenges because these agents are associated with cosmetic adverse effects, Hubbard says. Additionally, EGFR inhibitors could be reserved for later-line therapy since they have demonstrated activity in this space. 

The ongoing phase 2 PULSE trial (NCT03992456) is evaluating whether retreatment with the EGFR inhibitor panitumumab (Vectibix) is superior to standard treatment with regorafenib (Stivarga) or TAS-102 (trifluridine/tipiracil; Lonsurf) in patients with metastatic and/or unresectable 

 wild-type CRC. The results of this study could provide additional insight into whether retreatment with an EGFR inhibitor is a viable strategy for patients with CRC, concludes Hubbard.

Joleen M. Hubbard, MD, discusses sequencing challenges regarding EGFR inhibitors in colorectal cancer.  



Dr. Hubbard on Sequencing Challenges With EGFR Inhibitors in CRC 

Tanios S. Bekaii-Saab, MD, FACP, medical oncologist, medical director, Cancer Clinical Research Office, vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses indicators of progression in colorectal cancer (CRC).

Indicators of progression fit together like a puzzle to determine whether a patient has progressed and requires additional treatment, says Bekaii-Saab. Three main factors should be considered when determining progression: the patient’s symptoms, the results of their most recent scan, and their cancer markers. 

An increase in patient symptoms, including weight loss and pain, is a key indication of progression and should be relied on most, explains Bekaii-Saab. Scan results should be given second-highest priority, followed by changes in cancer markers, Bekaii-Saab adds. For example, a patient who has an inconclusive scan but is experiencing significant symptoms likely has disease progression. Conversely, a patient with minimal symptoms and clear scans whose cancer markers are increasing may not require subsequent therapy, concludes Bekaii-Saab. 

Tanios S. Bekaii-Saab, MD, FACP, discusses indicators of progression in colorectal cancer.  



Dr. Bekaii-Saab Discusses Indicators of Progression in CRC 

Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center, and senior physician at Dana-Farber Cancer Institute, as well as the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, discusses the FDA approval of nivolumab (Opdivo) and cabozantinib (Cabometyx) in metastatic renal cell carcinoma (mRCC). 

On January 22, 2021, the FDA approved the combination of cabozantinib and nivolumab for the frontline treatment of patients with advanced RCC. The regulatory decision was based on findings from the phase 3 CheckMate-9ER trial, which showed that the combination improved overall survival, progression-free survival, and overall response rate compared with sunitinib (Sutent) as frontline treatment for this patient population. Ultimately, the combination induced a 49% reduction in the risk of disease progression or death compared with sunitinib.

Moreover, during the 2020 ESMO Virtual Congress, health-related quality-of-life (QOL) data showed that patients who received cabozantinib plus nivolumab had significantly better QOL versus sunitinib.

Although other combinations of immunotherapy and VEGF inhibitors, including nivolumab plus ipilimumab (Yervoy), are approved in this space, the combination of cabozantinib/nivolumab is unique in that it demonstrated benefit across all patient subgroups, irrespective of International Metastatic RCC Database Consortium risk score, concludes Choueiri.

Toni K. Choueiri, MD, discusses the FDA approval of nivolumab and cabozantinib in metastatic renal cell carcinoma.  



Dr. Choueiri on the FDA Approval of Nivolumab/Cabozantinib in mRCC 

Daniel H. Ahn, DO, an oncologist, internist, and assistant professor of medicine at Mayo Clinic, discusses the growing role of circulating tumor DNA (ctDNA) in colorectal cancer (CRC).

The roles of ctDNA and minimal residual disease (MRD) are becoming more understood in CRC, as well as across all solid malignancies, says Ahn. Although additional investigation is warranted, MRD has the potential to be a prognostic and predictive biomarker for patient outcomes. Ultimately, MRD positivity confers a worse prognosis compared with MRD negativity, but questions remain as to how that influences treatment selection in patients with low-risk disease and in those who will receive adjuvant chemotherapy, Ahn explains.

Findings from a study, which were presented during the 2021 Gastrointestinal Cancers Symposium, showed that postoperative ctDNA positivity was more strongly associated with relapse-free survival compared with carcinoembryonic antigen (CEA). Ultimately, the results showed that ctDNA analysis can better predict the risk of recurrence compared with CEA and offers a reliable biomarker for treatment response monitoring. 

Daniel H. Ahn, DO, discusses the growing role of circulating tumor DNA in colorectal cancer.  



Dr. Ahn on the Growing Role of ctDNA as a Biomarker in CRC 

Balazs Halmos, MD, MS, director of the Multidisciplinary Thoracic Oncology Program and director of the Section of Thoracic Medical Oncology for Montefiore Health Systems, first director of Clinical Cancer Genetics and professor of clinical medicine at the Albert Einstein College of Medicine, discusses the emergence of KRAS-targeted therapies in lung cancer.

 mutations in lung cancer is an unfolding story, says Halmos. Efficacy data with KRAS inhibitors as single agents and in combination regimens with conventional first- and second-line options, such as chemotherapy and immunotherapy, will likely emerge in 2021, Halmos explains. 

 mutations are present in a significant proportion of patients with lung cancer, the field is hoping to develop an understanding of which investigational KRAS-directed therapy yields the most significant efficacy and in which specific patient populations, concludes Halmos. 

Balazs Halmos, MD, MS, discusses the emergence of KRAS-targeted therapies in lung cancer.  



Dr. Halmos on the Emergence of KRAS-Targeted Therapies in Lung Cancer

Howard A. “Skip” Burris, III, MD, FASCO, FACP, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, and a 2014 Giant of Cancer Care

 in Drug Development, discusses the potential of novel combination strategies with checkpoint inhibitors in oncology.

Ongoing trials are evaluating PD-L1 inhibitors in combination with novel therapies, such as TIGIT- and LAG-3–directed antibodies, says Burris. Early data have shown improved activity with combination regimens compared with single-agent checkpoint inhibitors. Additionally, these novel therapies appear to improve activity versus single-agent treatment in patients who have received prior checkpoint inhibitors, Burris explains. 

Moreover, these benefits have been observed across a wide section of oncology, including lung cancer, colon cancer, and melanoma, says Burris. As such, the potentially diverse application of these therapies is an exciting research effort to keep an eye on in 2021.

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses the potential of novel combination strategies with checkpoint inhibitors in oncology.  



Dr. Burris on the Potential for Novel Checkpoint Inhibitor Combinations in Oncology 

Yi Lin, MD, PhD, consultant, Division of Hematology, Department of Internal Medicine, consultant, Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, assistant professor of medicine and oncology, Mayo Clinic, discusses the importance of developing non-BCMA–targeting agents in multiple myeloma.

Multiple BCMA-directed CAR T-cell therapies, bispecific antibodies, and antibody-drug conjugates are demonstrating significant efficacy for patients with multiple myeloma. However, the field is developing non-BCMA–targeted options as well, Lin explains.

Early data with non-BCMA–targeting approaches are showing high rates of early responses in patients, says Lin. With the rapid growth of immunotherapy in multiple myeloma, data will likely emerge in the coming years showing that non-BCMA–directed therapies are good options for patients, concludes Lin. 

Yi Lin, MD, PhD, discusses the importance of developing non-BCMA–targeting agents in multiple myeloma. 



Dr. Lin on the Importance of Developing non-BCMA–Targeting Agents in Myeloma 

Shaji K. Kumar, MD, a consultant in the Division of Hematology and a professor of medicine with Mayo Clinic, discusses the emergence of minimal residual disease (MRD) negativity as a surrogate end point in relapsed/refractory multiple myeloma.

Progression-free survival (PFS) has served as the primary end point for multiple registrational clinical trials in  relapsed multiple myeloma, says Kumar. However, as older phase 3 trials continue to mature, overall survival data are beginning to emerge. 

Notably, many recent studies have demonstrated the importance of achieving MRD negativity in patients with multiple myeloma, Kumar explains. As such, MRD negativity is being considered as a surrogate end point in trials. Additionally, data have shown that MRD negativity is associated with improved PFS, further strengthening the notion that depth of response influences PFS, concludes Kumar.

Shaji K. Kumar, MD, discusses the emergence of minimal residual disease negativity as a surrogate end point in relapsed/refractory multiple myeloma.  



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