, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Cedars-Sinai Medical Center, we had the pleasure of speaking with Karen L. Reckamp, MD, about pragmatic oncology research. Dr Reckamp is a professor in medicine, medical oncology director of the Lung Institute, director of the Division of Medical Oncology, and associate director of Clinical Research at Cedars-Sinai Medical Center in Los Angeles, California. 

In our exclusive interview, Dr Reckamp discussed the definition of pragmatic clinical trials, how the phase 3 S2302 Pragmatica-Lung trial (NCT05633602) exemplifies the goals of these types of studies, and ways that clinical trial investigators can make their research more pragmatic.

That’s all we have for today! Thank you for listening to this episode of 

, sponsored by Cedars-Sinai Medical Center. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.

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Podcasts

Dr Reckamp discusses the definition of pragmatic clinical trials and ways that clinical trial investigators can make their research more pragmatic.

Reckamp Discusses the Integration of Pragmatic Elements Into Oncology Clinical Trial Designs

Karen Reckamp, MD, professor, medicine; director, Division of Medical Oncology, Cedars-Sinai Medical Center, compares capmatinib (Tabrecta) and tepotinib (Tepmetko), 2 drugs that are approved for the treatment of 

 exon 14–mutated non–small cell lung cancer (NSCLC).

Capmatinib and tepotinib have similar efficacy and toxicity profiles, so deciding between them should be a patient-centered choice, Reckamp says. Importantly, both agents demonstrate evidence of central nervous system activity, Reckamp notes.

Additionally, peripheral edema is the primary adverse effect of both tepotinib and capmatinib, Reckamp explains. Where these 2 drugs differ the most is in their dosing schedule: twice daily dosing is recommended for capmatinib, whereas once daily dosing is recommended for tepotinib, a schedule which may improve patient compliance with treatment.

Videos

Karen Reckamp, MD, compares capmatinib and tepotinib, 2 drugs that are approved for the treatment of MET exon 14–mutated non–small cell lung cancer.

Dr. Reckamp on Treatment Decisions in MET Exon 14–Mutated NSCLC

Karen L. Reckamp, MD, director, Medical Oncology, associate director, Clinical Research, medical oncology director, Lung Institute, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, discusses the significance of the final results of the ALTA studies in ALK-positive non–small cell lung cancer (NSCLC).

During the 2021 ASCO Annual Meeting, the final results of the ALTA trial demonstrated sustained long-term activity with brigatinib (Alunbrig) in patients with ALK-positive, crizotinib (Xalkori)-refractory NSCLC.

In the phase 1/2 study, the median progression-free survival (PFS) was 14.5 months in all patients with a median follow-up of 27.7 months. The last patient was enrolled on the study 5.6 years prior to the final results. In arm B of the ALTA trial, the median PFS was 16.7 months with a median follow-up of 28.3 months. The last patient was enrolled 4.4 years prior to the final results of the study. 

Although crizotinib is no longer typically utilized in the frontline setting for patients with 

-positive NSCLC, understanding the long-term durability of responses with brigatinib in this patient population is important, says Reckamp. 

-altered NSCLC is relatively rare, so determining the optimal sequencing of the multiple, efficacious ALK inhibitors available in this setting is clinically meaningful, Reckamp concludes.

Karen L. Reckamp, MD, discusses the significance of the final results of the ALTA trial in patients with ALK-positive non–small cell lung cancer.



Dr. Reckamp on the Significance of ALTA in ALK+ NSCLC 

Karen Reckamp, MD, co-director, Lung Cancer and Thoracic Oncology Program, medical director, Clinical Research Operations, professor, Department of Medical Oncology & Therapeutics Research, thoracic oncologist, discusses current and emerging therapeutic strategies to target 

-targeting strategies for lung cancer have been explored for quite some time, but early studies were negative likely due to patient selection and lack of understanding of the complexities of the MET signaling pathway, Reckamp says. Now, it is known that MET is important in direct signaling through other pathways and can also connect with other tyrosine kinase pathways. It can also result in resistance mechanisms and activation of other pathways, she says.

Therefore, direct MET inhibition may not be as effective. Researchers have identified mutations and amplification, including the 

 exon 14 skipping mutation. Regarding agents, crizotinib (Xalkori) leads to an approximate 40% response rate in these patients. In May 2018, the FDA granted crizotinib a breakthrough therapy designation for the treatment of patients with metastatic NSCLC with 

 exon 14 alterations who progress after receiving platinum-based chemotherapy.

Beyond crizotinib, investigators are looking to target more patients through 

. Combination or multi-targeted therapies have shown that targeting

 can be beneficial in wild-type patients, as well. Novel agents such as bispecific antibodies are being explored to overcome resistance, such as resistance to osimertinib (Tagrisso) in those who develop 

Karen Reckamp, MD, co-director, Lung Cancer and Thoracic Oncology Program, medical director, Clinical Research Operations, professor, Department of Medical Oncology & Therapeutics Research, thoracic oncologist, discusses current and emerging therapeutic strategies to target MET in non-small cell lung cancer.

Dr. Reckamp on MET-Targeting Strategies in NSCLC

Karen L. Reckamp, MD, co-director, Lung Cancer and Thoracic Oncology Program, associate professor, City of Hope, discusses the results of a phase II study of the AKT inhibitor MK-2206 plus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) who progressed on erlotinib.

One cohort on this study consisted of patients with EGFR wild-type disease who had previously responded to EGFR TKI therapy for at least 12 weeks. The other cohort on the study consisted of patients with EGFR mutant disease who had responded to EGFR TKI therapy for at least 12 weeks. Patients with EGFR wild-type disease saw an improvement in disease control rate when treated with MK-2206 in combination with erlotinib.

This combination may improve de novo resistance and may be beneficial for patients with EGFR wild-type disease.

Karen L. Reckamp, MD, discusses the results of a phase II study of the AKT inhibitor MK-2206 plus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) who progressed on erlotinib.

Dr. Reckamp on MK-2206 for the Treatment of EGFR Wild-Type NSCLC

Karen Reckamp, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California, discusses a phase II study that evaluated the efficacy of the pretreatment serum test VeriStrat at predicting response to erlotinib (Tarceva) plus high-dose celecoxib (Celebrex) for patients with advanced non-small cell lung cancer (NSCLC).

The study randomized 107 patients with advanced NSCLC to receive erlotinib plus high-dose celecoxib or erlotinib and placebo. VeriStrat classifications were received for 96 patients and found a significant correlation between a Good VeriStrat status and disease control rate. Additionally, Good classifications more accurately predicted response and progression-free survival for patients receiving the combination of erlotinib and celecoxib, compared to erlotinib alone.

Reckamp is unsure why the VeriStrat analysis was more effective for the combination arm, since it has been validated for erlotinib alone. Overall, these results call for further trials to validate Veristrat's ability to determine which patients will benefit the most from the addition of high-dose celecoxib

View coverage from the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology

Dr. Karen Reckamp, from City of Hope, evaluates the predictive efficacy of the pretreatment serum test VeriStrat for non-small cell lung cancer.

Dr. Reckamp Evaluates the Predictive Efficacy of VeriStrat

Karen Reckamp, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California, discusses use of heat shock protein 90 (Hsp90) inhibition in multiple signaling pathways.

Rechamp explains that Hsp90 is being investigated not only in ALK translocated patients but also in more general uses. She describes the next step for clinical investigation is the combination of the proteins with other targeted agents such as erlotinib and gefitinib in lung cancer.

Dr. Karen Reckamp from the City of Hope Cancer Center Discusses the Use of Hsp90 Inhibitors

Dr. Reckamp Discusses the Use of Hsp90 Inhibitors

Karen Reckamp, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California, describes the various clinical studies currently underway examining the use of heat shock proteins.

Clinical trials are currently looking specifically at ALK translocated, crizotinib resistance, and patient that have not yet received crizotinib. Further examination is being completed into heat shock proteins in combination with docetaxel and other targets and biomarkers that specify which patients will have the most benefit.

Dr. Karen Reckamp City of Hope cancer center on Current Heat Shock Protein Clinical Trials

Dr. Reckamp on Current Heat Shock Protein Clinical Trials

Karen Reckamp, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California, describes early studies in lung cancer that examine heat shock proteins as single agents, specifically in ALK translocated patients and some EGFR wild type adenocarcinoma patients, which are less well defined. The proteins have shown success when used as a single agent when there is a resistance to crizotinib. Studies are currently underway that are investigating heat shock proteins in chemotherapy combination therapies.

Dr. Karen Reckamp from City of Hope Cancer Center Describes the Use of Heat Shock Proteins

Dr. Reckamp Describes the Use of Heat Shock Proteins

Karen Reckamp, MD, MS, assistant professor, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California, discusses the use of heat shock proteins in the treatment of lung cancer.

Reckamp explains that heat shock proteins act as chaperone proteins that permit oncoproteins to function. The proteins work as an alternative to inhibiting the tyrosine kinase pathway and are involved in multiple lung cancer related signalling pathways such as EGFR, RAS, ALK, and MET. Heat shock proteins can be used when resistance to other methods are developed.

Dr. Karen Reckamp from City of Hope Cancer center Discusses Heat Shock Proteins in Lung Cancer

Karen Reckamp, MD

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