Nathan Pennell, MD, PhD, a medical oncologist and director of the Lung Cancer Medical Oncology Program at the Taussig Cancer Institute of Cleveland Clinic, discusses challenges with next-generation sequencing (NGS) in lung cancer.

Part of the challenge with access to next-generation sequencing (NGS) in the lung cancer space is inertia, says Pennell. Some institutions already have single-gene testing in place, although many do not know what tests their pathology department specifically uses. Many times, tests are sent out to external vendors that utilize different testing techniques. However, NGS should be broadly available—especially in lung cancer, Pennell emphasizes.

Multiple FDA-approved vendors and assays are available within the space that can look for all of the guideline-suggested targets. As such, access to NGS should no longer be a barrier, says Pennell. However, other barriers to using NGS exist, such as having enough tissue and ensuring that there is sufficient turnaround time in order to inform decisions on how to treat patients. 

There is work to be done, not just in raising awareness of this approach, but also ensuring that institutions have the right infrastructure in place to provide testing to all eligible patients and to receive the results in a timely fashion. The truth is that there is no reason that NGS should not be universally used in lung cancer, concludes Pennell.

Videos

Nathan Pennell, MD, PhD, discusses challenges with next-generation sequencing in lung cancer.

Dr. Pennell on Challenges With NGS in Lung Cancer

A. Oliver Sartor, MD, a professor of medicine and the medical director of the Tulane Cancer Center and the Bernadine Laborde Professor of Cancer Research in the Department of Urology at Tulane University, discusses the significance of the REASSURE trial in patients with metastatic castration-resistant prostate cancer.

In the global observational trial, investigators are examining the safety of radium-223 dichloride (Xofigo) in routine clinical practice over 7 years of follow up in this patient population. A second prespecified interim analysis of the trial focused on outcomes of patients who received lutetium-177 PSMA-617 (177Lu-PSMA) following radium-223. What was understood from the study of this registry is that a series of patients did receive sequential radiopharmaceuticals—alpha and beta particles, which were given in sequence, says Sartor. This is important because no prior data are available on this. Although it is difficult to discern whether there was activity with the approach, no safety signals were identified, adds Sartor.

The results from the trial presented during the 

 are not particularly exciting, Sartor explains, they are still important in that they indicate that 177Lu-PSMA and radium-223 can be used sequentially without undo harm. Prospective trials will need to be conducted to properly determine which patients might or might not benefit from this approach and whether any toxicities that were not recognized do exist, says Sartor. This research is very preliminary, but it is the first step, that is what makes it important, concludes Sartor.

Oliver Sartor, MD, discusses the significance of the REASSURE trial in patients with metastatic castration-resistant prostate cancer.

Dr. Sartor on the Significance of the REASSURE Trial in mCRPC

Naval G. Daver, MD, an associate professor in the Department of Leukemia within the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses updated findings on the combination of investigational CD47-directed antibody magrolimab (formerly 5F9) and azacitidine in myelodysplastic syndrome (MDS).

Results from the phase 1b study were delivered during the 

2020 European Hematology Association Congress

, says Daver. A total of 39 evaluable patients with MDS were enrolled at the time of the data cutoff; these were all intermediate- to very high-risk patients with Revised International Prognostic Scoring System risk for MDS criteria. In fact, a large proportion of these patients, 64%, had poor-risk cytogenetics for MDS criteria, and the median age was around 70 years. In general, these factors were indicative of a high-risk patient population, Daver adds.

Results showed an objective response rate of 91%, which is very encouraging for such a high-risk MDS population, says Daver. True complete remission (CR) rate, which is a CR with full count recovery, was 42%. Interestingly, as treatment continued in patients beyond 6 months, which was the majority of the patients, the true CR rate increased to 56%. What that shows is that with continued exposure to the combination, there was better adjustment, count recovery, and more patients were able to achieve a CR, which is the ideal goal of treatment, concludes Daver.

Naval G. Daver, MD, discusses updated findings on the combination of the investigational CD47-directed antibody magrolimab and azacitidine in myelodysplastic syndrome.

Dr. Daver on Updated Findings With Magrolimab/Azacitidine in MDS

Charles M. Rudin, MD, PhD, medical oncologist, chief, Thoracic Oncology Service, co-director, Druckenmiller Center for Lung Cancer Research, Sylvia Hassenfeld Chair in Lung Cancer Research, Memorial Sloan Kettering Cancer Center, discusses the design of the phase 3 KEYNOTE-604 trial in extensive-stage small cell lung cancer (ES-SCLC).

In June 2019, the FDA approved pembrolizumab for the treatment of patients with metastatic SCLC who experience disease progression on or after platinum-based chemotherapy and at least 1 prior line of therapy.

KEYNOTE-604 evaluated whether pembrolizumab plus etoposide and platinum induced an improved response compared with placebo as first-line treatment for patients with ES-SCLC, says Rudin.

Findings from the study showed that the PD-1 inhibitor plus chemotherapy significantly improved progression-free survival compared with placebo.

Charles M. Rudin, MD, PhD, discusses the design of the phase 3 KEYNOTE-604 trial in extensive-stage small cell lung cancer. 

Dr. Rudin on the Design of the KEYNOTE-604 Trial in ES-SCLC

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 importance of identifying biomarkers in advanced non–small cell lung cancer (NSCLC).

In patients with advanced NSCLC, biomarker testing should be a routine practice, says Halmos. Moreover, it is important to perform broad panel testing rather than test for a few select genetic alternations, Halmos adds.

There are currently 8 markers that patients should be tested as there are targeted therapies that are available for patients who test positive, Halmos says. These include 

 is an emerging marker for which investigational targeted therapy directed at 

G12C has demonstrated clinical activity, Halmos explains. Identifying actionable biomarkers in NSCLC may inform treatment selection in patients or indicate clinical trials for which the patient may be eligible for, Halmos concludes.

Balazs Halmos, MD, MS, discusses the importance of identifying biomarkers in advanced non–small cell lung cancer. 

Dr. Halmos on the Importance of Identifying Biomarkers in Advanced NSCLC

Alexander M. M. Eggermont, MD, PhD, professor of oncology, University of Paris-Sud, professor of oncological surgery, chair, International Research Network on Cancer, Erasmus University of Rotterdam, Joseph Maisin Honorary Chair of Oncological Surgery, Louvain Catholic University, discusses responses to adjuvant pembrolizumab (Keytruda) in patients with different subtypes of stage III melanoma.

Within stage III melanoma, there is stage IIIA disease, which encompasses microscopic lymph node involvement, IIIB disease, and IIIC disease, says Eggermont.

In updated findings from the phase 3 EORTC 1325-MG/KEYNOTE-054 trial, pembrolizumab (Keytruda) showed consistently better rates of recurrence-free survival (RFS) compared with placebo across stage III subtypes, explains Eggermont. Moreover, at a 3-year median follow-up, the hazard ratios with pembrolizumab were 0.50 in stage IIIA disease, 0.56 in IIIB disease, and 0.57 in IIIC disease. Additionally, RFS rates were 81.2%, 65.7%, and 54.3%, respectively.

These findings add to the discussion of whether pembrolizumab should be considered for patients with stage IIIA disease, concludes Eggermont.

Alexander M. M. Eggermont, MD, PhD, discusses responses to adjuvant pembrolizumab in patients with different subtypes of stage III melanoma. 

Dr. Eggermont on Responses to Adjuvant Pembrolizumab in Stage III Melanoma Subtypes

Michael J. Morris, MD, medical oncologist, clinical director of Genitourinary Medical Oncology Service, and Prostate Cancer Section Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, discusses the ​design of the phase 3 CONDOR trial in men with biochemically recurrent prostate cancer.

​The study evaluated the investigational, urea-based prostate specific membrane antigen (PSMA)-targeted PET radiopharmaceutical 18F-DCFPyL-PET/CT, says Morris.

Eligible patients had to have biochemically relapsed disease following radical prostatectomy or definitive radiation therapy, Morris explains. 

Historically, this has been a challenging patient population to study because patients need to have negative standard imaging. In this trial, patients had to undergo standard imaging with a CT scan, MRI, bone scan, or fluciclovine to obtain negative or noninformative results prior to enrollment, Morris explains.

Michael J. Morris, MD, discusses the ​design of the phase 3 CONDOR trial in men with biochemically recurrent prostate cancer.

Dr. Morris on the Design of the Phase 3 CONDOR Trials in Recurrent Prostate Cancer

Nancy U. Lin, MD, associate professor of medicine at Harvard Medical School; associate chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers; director of the Metastatic Breast Cancer Program and senior physician at Dana-Farber Cancer Institute, discusses the development of systemic therapies for the treatment of patients with metastatic HER2-positive breast cancer and brain metastases.

At least half of patients with HER2-positive metastatic breast cancer will develop brain metastases over the course of their disease, says Lin. However, there weren't any approved agents for the systemic treatment of patients with brain metastases until recently. 

Several trials evaluating HER2-directed TKIs such as lapatinib (Tykerb) and neratinib (Nerlynx) demonstrated objective responses in the central nervous system, explains Lin. However, the phase 2 HER2CLIMB study was the first randomized trial to demonstrate an overall survival benefit for patients with brain metastases.

Additionally, the study opened the discussion of including patients with brain metastases in future clinical trials, which is currently an unmet need in this space, concludes Lin.

Nancy U. Lin, MD, discusses the development of systemic therapies for the treatment of patients with metastatic HER2-positive breast cancer and brain metastases.

Dr. Lin on Developing Systemic Therapies for Patients with Brain Metastases in HER2+ Breast Cancer 


Paolo Ghia, MD, PhD, a professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Università Vita-Salute San Raffaele University, discusses the efficacy and safety of acalabrutinib (Calquence) in the phase 3 ASCEND trial in relapsed/refractory chronic lymphocytic leukemia (CLL). 

Final data from the trial were presented at the 

, and showed favorable efficacy with acalabrutinib over the physician’s choice of rituximab (Rituxan) in combination with either idelalisib (Zydelig) or bendamustine. Acalabrutinib is a second-generation BTK inhibitor, and BTK inhibition is a mainstay in the treatment of patients with CLL, says Ghia. Acalabrutinib appears to be very effective when compared with novel agent, such as idelalisib, plus rituximab, or a standard chemotherapy, such as bendamustine, plus rituximab. The data observed with acalabrutinib are comforting and prove that this agent is another tool that can be added to the treatment armamentarium, says Ghia.

Additionally, acalabrutinib showed a favorable toxicity profile and appeared to be safer than the combination of idelalisib plus rituximab, with a lower frequency of treatment discontinuation, concludes Ghia.

Paolo Ghia, MD, PhD, discusses the efficacy and safety of acalabrutinib in the phase 3 ASCEND trial in relapsed/refractory chronic lymphocytic leukemia.

Dr. Ghia on Efficacy and Safety of Acalabrutinib in Relapsed/Refractory CLL

Gaël Roué, PhD, senior scientist at Josep Carreras Leukaemia Research Institute, discusses interest regarding the novel irreversible inhibitor TG-1701 in models of ibrutinib (Imbruvica)-resistant mantle cell lymphoma (MCL).

 tested the activity of TG-1701 when combined with ublituximab and umbralisib in ibrutinib-resistant MCL. Interest in TG-1701 comes from the fact that there is a large interest regarding BTK inhibitors for B-cell malignancies, says Roué. This is due to the fact that most first- or second-generation molecules have nonspecific activity but could impact other signals within the tumor B-cells. This molecule draws a lot of interest within the MCL space as it is more specific to the BTK pathway, explains Roué.

Another point of interest is that when investigators compared the second-generation molecule with the first-in-class inhibitor, ibrutinib, they found that some activity was retained in cases of resistance to ibrutinib, concludes Roué.

Gaël Roué, PhD, discusses interest regarding the novel irreversible inhibitor TG-1701 in models of ibrutinib (Imbruvica)-resistant mantle cell lymphoma.

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