POPULARITY
In this episode, listen to Alice T. Shaw, MD, PhD, and Jessica J. Lin, MD, share their thoughts on the available and emerging clinical data for second-line and beyond treatments in patients with recurrent ROS1-altered advanced NSCLC including:Assessing ROS1-TKI resistance mutations with tumor and liquid biopsies in patients with ROS1-altered advanced NSCLCPrevious TKI-treated cohort from the TRIDENT-1 study: efficacy of repotrectinib in patients with recurrent ROS1-altered NSCLC and measurable baseline brain metastases Phase II TRUST-1 trial of taletrectinib: activity in patients with known ROS1 G2032R resistance mutation ROS1-altered advanced NSCLCThe global phase I/II ARROS-1 study of zidesamtinib (NVL-520): safety summary in patients with ROS1-altered advanced NSCLC Program faculty:Jessica J. Lin, MDAttending PhysicianMassachusetts General HospitalAssociate Professor of MedicineHarvard Medical SchoolBoston, MassachusettsAlice T. Shaw, MD, PhDChief, Strategic PartnershipsAttending Physician, Thoracic OncologyDana-Farber Cancer InstituteHarvard Medical SchoolBoston, MassachusettsResources:To download the slides associated with this podcast discussion, please visit the program page.
In this episode, listen to Alice T. Shaw, MD, PhD, and Jessica J. Lin, MD, share their thoughts on the available clinical data in support of frontline treatments for ROS1-altered NSCLC including:Efficacy and safety data for crizotinib, entrectinib, and repotrectinib in patients with ROS1-altered advanced NSCLCLong-term safety observations for crizotinib and entrectinib CNS activity of entrectinib and repotrectinib in patients with brain metastasesRepotrectinib activity in ROS1-TKI resistance mutations Program faculty:Jessica J. Lin, MDAttending PhysicianMassachusetts General HospitalAssociate Professor of MedicineHarvard Medical SchoolBoston, MassachusettsAlice T. Shaw, MD, PhDChief, Strategic PartnershipsAttending Physician, Thoracic OncologyDana-Farber Cancer InstituteHarvard Medical SchoolBoston, MassachusettsResources:To download the slides associated with this podcast discussion, please visit the program page.
Seminal Trial Series: Crizotinib in PROFILE 1001 by IASLC
Which drug keeps lung cancer from progressing for over 5 years? Find out about this and more in today's PeerDirect Medical News Podcast.
A new editorial paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Latest updates on MET targeted therapy for EXON 14 mutations in lung cancer.” In their new editorial, researchers Mira Al Jaberi, Wolfgang Clough and Samir Dalia from Mercy Hospital discuss the MET gene. Several alterations in the MET gene were identified as targetable oncogenic changes leading to non-small cell lung cancer (NSCLC). These include genomic amplifications, exon 14 skipping mutations and fusion. Capmatinib has been considered as a first-line treatment for patients with NSCLC carrying a MET exon 14 skipping mutation since May 2020 by the USFDA. A study newly published in early 2023 showed that Crizotinib, a tyrosine kinase inhibitor, was also effective for MET fusions, which occur rarely in 0.2–0.3% of patients with lung cancer. A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance. “A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance [4, 5].” Several structurally different MET tyrosine kinase inhibitors (TKIs) have been developed or are under clinical evaluation. TKIs are categorized into type I TKIs (type Ia: crizotinib; type Ib: savolitinib, capmatinib) and type II TKIs (cabozantinib, glesatinib, merestinib). Combination therapy reduces resistance and enhances clinical outcomes. “These clinical trials along with others will show us if other MET inhibitors or combination therapy may be better than the current standard of care.” DOI - https://doi.org/10.18632/oncotarget.28419 Correspondence to - Samir Dalia - samir.dalia@mercy.net Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28419 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, non small cell lung cancer, MET mutation, targeted therapy, precision medicine About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Drs Sumanta Pal and Mehmet Asim Bilen discuss the complexities of treating patients with non–clear cell renal carcinoma, the nuances of rare subtypes, and when to use chemotherapy vs immunotherapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968741). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma https://emedicine.medscape.com/article/281340-overview Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology https://pubmed.ncbi.nlm.nih.gov/34991070/ PAPMET Trial: Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed https://clinicaltrials.gov/ct2/show/NCT02761057 Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non–Clear-Cell Renal Cell Carcinoma and Genomic Correlates https://ascopubs.org/doi/10.1200/JCO.21.01944 Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605393/ Cabozantinib Plus Nivolumab Phase I Expansion Study in Patients With Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy https://aacrjournals.org/clincancerres/article/28/7/1353/682207/Cabozantinib-plus-Nivolumab-Phase-I-Expansion Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study https://ascopubs.org/doi/10.1200/JCO.21.00939 A Single-Arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients With Advanced Non–Clear Cell Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/33867192/ ESMO 2022 https://www.esmo.org/meetings/esmo-immuno-oncology-congress-2022/abstracts Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma. The SAVOIR Phase 3 Randomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2766797 SAMETA: An Open-Label, Three-Arm, Multicenter, Phase III Study of Savolitinib + Durvalumab Versus Sunitinib and Durvalumab Monotherapy in Patients With MET-Driven, Unresectable, Locally Advanced/Metastatic Papillary Renal Cell Carcinoma (PRCC). https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.TPS4601 A Phase II Trial of Doxorubicin and Gemcitabine in Renal Cell Carcinoma With Sarcomatoid Features: ECOG 8802 https://pubmed.ncbi.nlm.nih.gov/21298497/ A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER) https://clinicaltrials.gov/ct2/show/NCT03141177
Drs Sumanta Pal and Tian Zhang review the state of the data on adjuvant treatment with immunotherapy for patients with renal cell carcinoma, including where current clinical trials stand. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968737). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study https://clinicaltrials.gov/ct2/show/NCT03793166 The Role of Targeted Therapy in the Management of High-Risk Resected Kidney Cancer: What Have We Learned and How Will It Inform Future Adjuvant Trials https://journals.lww.com/journalppo/Abstract/2020/09000/The_Role_of_Targeted_Therapy_in_the_Management_of.3.aspx Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy https://www.nejm.org/doi/10.1056/NEJMoa1611406 Sutent (sunitinib) prescribing information https://labeling.pfizer.com/showlabeling.aspx?id=607 Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma (KEYNOTE-564) https://www.nejm.org/doi/full/10.1056/NEJMoa2106391 RAMPART: A Phase III Multi-arm Multi-stage Trial of Adjuvant Checkpoint Inhibitors in Patients With Resected Primary Renal Cell Carcinoma (RCC) at High or Intermediate Risk of Relapse https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520913/ A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy (IMmotion010) https://clinicaltrials.gov/ct2/show/NCT03024996 A Comparison of Sunitinib with Cabozantinib, Crizotinib, and Savolitinib for Treatment of Advanced Papillary Renal Cell Carcinoma: a Randomised, Open-Label, Phase 2 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687736/ A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney (CheckMate 914) https://clinicaltrials.gov/ct2/show/NCT03138512 PROSPER: Phase III RandOmized Study Comparing PERioperative nivolumab versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN EA8143). https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.TPS4596 Pembrolizumab as Post Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Results From 30-Month Follow-up of KEYNOTE-564 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.290 Leibovich RCC Model: Prediction of Progression After Radical Nephrectomy for patients With Clear Cell Renal Cell Carcinoma https://cancernomograms.com/nomograms/972 Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results From ASSURE, ECOG 2805 https://aacrjournals.org/clincancerres/article/21/18/4048/117759/Effects-of-Adjuvant-Sorafenib-and-Sunitinib-on
FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)
Listen to a soundcast of the July 14, 2022 FDA approval of Xalkori (crizotinib) for ALK-positive inflammatory myofibroblastic tumor.
A new study has helped to define MET amplification as a rare but potentially actionable driver for non-small cell lung cancer (NSCLC). The paper, titled “Crizotinib in Patients With MET-Amplified NSCLC,” published in the Journal of Thoracic Oncology, introduces a third means of defining NSCLC subsets that can be targeted with a specific drug. In this episode, journalist Peter Goodwin interviews study author D. Ross Camidge, MD, PhD, Director of Thoracic Oncology at the University of Colorado School of Medicine, on the recent findings.
“To be a scientist,” notes Steve Morris, MD, “you have to take failure after failure with undying enthusiasm.” Without that persistence, we might never have had the lung cancer drug Crizotinib. The path to that drug’s development spanned more than two decades, and Dr. Morris played a critical and recurring role. In 1994, Dr. Morris and his team discovered the gene ALK and showed that it plays a critical role in some lymphomas. He went on to help show that a variety of cancer sub-types are caused by ALK abnormalities, including certain lung cancers, lymphomas, leukemias, mesotheliomas, thyroid cancers, and pediatric cancers. But he didn’t stop with discovery. He and his team also created a diagnostic test, the Vysis ALK Break Apart FISH Probe Kit, to help clinicians determine if a patient’s tumors have an abnormal ALK gene. Ultimately his efforts helped drug developers to come up with the lung cancer drug Xalkori (crizotinib), which was first approved by the FDA in 2011 for the treatment of ALK-positive non-small cell lung cancer. The drug’s use has been expanded since. Crizotinib is also being evaluated as a potential targeted drug therapy in the treatment of neuroblastoma, a type of brain cancer, and other cancers with ALK mutations or rearrangements. Up to 15% of neuroblastomas have mutations in the ALK gene. Steve Morris, MD, is the co-founder of Insight Genetics and serves as Chief Medical Officer for companies developing cancer therapies. Prior to that he was a Full Member at St. Jude Children’s Research Hospital. 4:49 – On his team’s “time-consuming, labor-intensive, capital-intensive” discovery of the ALK gene 8:48 – How ALK plays a role in cancer 11:20 – The road to making ALK a druggable target 16:58 – The diagnostic test he and his team developed to help clinicians determine if a patient’s tumors have an abnormal ALK gene 26:19 – On why he left academic medicine to pursue drug development and the creation of diagnostic tests 29:32 – On the challenges of drug development, including the low success rate, the long development timeline, and the very high capital investment 32:52 – On the exciting prospects of precision medicine 38:39 – The role of American Cancer Society funding on his career and the discovery of ALK
MUNICH— Anaplastic lymphoma kinase (ALK) inhibitors are as effective in “real world” clinical use for treating patients with non-small cell lung cancer (NSCLC) who test positive for ALK gene rearrangements as they are in clinical studies—even though randomized trials “cherry …Mohammad Jahanzeb AJ0
Dr Scagliotti speaks to ecancertv at ESMO 2016 about results from the confirmatory phase III trial ASCEND-5. He summarises these results, confirming the benefit of ceritinib for lung cancer patients with ALK rearrangements who had previously received crizotinib, and goes on to consider the impact of kinase inhibitor therapy.
Dr Scagliotti presents, at a press conference at ESMO 2016, results from the ASCEND-5 trial of ceritinib, a kinase inhibitor targeting ALK rearrangements, for patients with advanced non-small cell lung cancer who had relapsed following crizotinib therapy.
Dr Shaw presents, at a press conference at ASCO 2017, findings from a phase III clinical trial that point to a more effective initial treatment for patients with ALK-positive non-small cell lung cancer.
Dr Shaw speaks with ecancer at ASCO 2017 about results from the ALEX trial of alectinib, a next-generation ALK inhibitor, for patients with lung cancer containing ALK mutations. She describes the significant benefits of alectinib over crizotinib, with progression free survival at 25.7 months compared to 10.4 months, fewer side effects and a reduced incidence of brain metastases. Overall, Dr Shaw encourages the use of alectinib as the new standard of care, and for doctors to discuss its use with patients currently receiving crizotinib.
COPENHAGEN—Longer progression free survival (PFS) was achieved in patients with ALK-rearranged non-small cell lung cancer (NSCLC) previously treated with crizotinib randomised to treatment with the second generation anaplastic lymphoma kinase (ALK) inhibitor ceritinib rather than chemotherapy in the phase 3 …161207-esmo-giorgio-scagliotti-ajo-production-master
Eric Haura describes the identification of new targets for treating lung cancers driven by ALK fusion proteins.
Dr. Ross Camidge, University of Colorado, addresses the question of whether to use a second generation ALK inhibitor as first line therapy or only after acquired resistance to crizotinib.
Dr. Ross Camidge, University of Colorado, addresses the question of whether to use a second generation ALK inhibitor as first line therapy or only after acquired resistance to crizotinib.
Dr. Ross Camidge, University of Colorado, addresses the question of whether to use a second generation ALK inhibitor as first line therapy or only after acquired resistance to crizotinib.
Dr. Ross Camidge, University of Colorado, discusses management of CNS progression for ALK-positive NSCLC including monitoring frequency and preferences between systemic and radiation therapy.
Dr. Ross Camidge, University of Colorado, discusses management of CNS progression for ALK-positive NSCLC including monitoring frequency and preferences between systemic and radiation therapy.
Dr. Ross Camidge, University of Colorado, discusses management of CNS progression for ALK-positive NSCLC including monitoring frequency and preferences between systemic and radiation therapy.
Dr. Ross Camidge, University of Colorado, describes the second generation ALK-inhibitors which provide good options for ALK-positive NSCLC patients who have developed acquired resistance to crizotinib.
Dr. Ross Camidge, University of Colorado, describes the second generation ALK-inhibitors which provide good options for ALK-positive NSCLC patients who have developed acquired resistance to crizotinib.
Dr. Ross Camidge, University of Colorado, describes the second generation ALK-inhibitors which provide good options for ALK-positive NSCLC patients who have developed acquired resistance to crizotinib.
Dr. Ross Camidge, University of Colorado, explains the preference for crizotinib rather than platinum doublet chemotherapy as first line treatment for patients with ALK or ROS1 rearrangements.
Dr. Ross Camidge, University of Colorado, explains the preference for crizotinib rather than platinum doublet chemotherapy as first line treatment for patients with ALK or ROS1 rearrangements.
Dr. Ross Camidge, University of Colorado, explains the preference for crizotinib rather than platinum doublet chemotherapy as first line treatment for patients with ALK or ROS1 rearrangements.
Dr. Ross Camidge, University of Colorado, describes ROS-1 rearrangements and compares them to ALK rearrangements in frequency of occurrence and response to treatment.
Dr. Ross Camidge, University of Colorado, describes ROS-1 rearrangements and compares them to ALK rearrangements in frequency of occurrence and response to treatment.
Dr. Ross Camidge, University of Colorado, describes ROS-1 rearrangements and compares them to ALK rearrangements in frequency of occurrence and response to treatment.
Dr. Heather Wakelee, Stanford University Medical Center, evaluates the lack of evidence for the use of targeted therapies after surgery, and describes ongoing trials attempting to resolve that issue.
Dr. Heather Wakelee, Stanford University Medical Center, evaluates the lack of evidence for the use of targeted therapies after surgery, and describes ongoing trials attempting to resolve that issue.
Dr. Heather Wakelee, Stanford University Medical Center, evaluates the lack of evidence for the use of targeted therapies after surgery, and describes ongoing trials attempting to resolve that issue.
Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, describes the types of situations in which local therapy is appropriate for treating limited acquired resistance.
Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, describes the types of situations in which local therapy is appropriate for treating limited acquired resistance.
Dr. Jared Weiss, UNC Lineberger Comprehensive Cancer Center, describes the types of situations in which local therapy is appropriate for treating limited acquired resistance.
Dr. Nathan Pennell, Cleveland Clinic, discusses acquired resistance to Xalkori in ALK-positive patients, and second generation inhibitors designed to overcome that resistance, such as Zykadia and alectinib.
Dr. Nathan Pennell, Cleveland Clinic, discusses acquired resistance to Xalkori in ALK-positive patients, and second generation inhibitors designed to overcome that resistance, such as Zykadia and alectinib.
Dr. Nathan Pennell, Cleveland Clinic, discusses acquired resistance to Xalkori in ALK-positive patients, and second generation inhibitors designed to overcome that resistance, such as Zykadia and alectinib.
Dr. Nathan Pennell, Cleveland Clinic, describes other options for treatment of acquired resistance, including chemotherapy, ablation with SBRT and a combination of Gilotrif and Erbitux.
Dr. Nathan Pennell, Cleveland Clinic, describes other options for treatment of acquired resistance, including chemotherapy, ablation with SBRT and a combination of Gilotrif and Erbitux.
Dr. Nathan Pennell, Cleveland Clinic, describes other options for treatment of acquired resistance, including chemotherapy, ablation with SBRT and a combination of Gilotrif and Erbitux.
Dr. Nathan Pennell, Cleveland Clinic, reviews the available trial evidence for the use of targeted therapies in the post-operative/adjuvant setting.
Dr. Nathan Pennell, Cleveland Clinic, reviews the available trial evidence for the use of targeted therapies in the post-operative/adjuvant setting.
Dr. Nathan Pennell, Cleveland Clinic, reviews the available trial evidence for the use of targeted therapies in the post-operative/adjuvant setting.
Xalkori (critzotinib) was the first approved treatment for ALK+ and ROS1 lung cancer. Since then, other drugs have been approved or are currently undergoing scientific review. In this video, Dr. Owonikoko outlines these options for patients.
Xalkori (critzotinib) was the first approved treatment for ALK+ and ROS1 lung cancer. Since then, other drugs have been approved or are currently undergoing scientific review. In this video, Dr. Owonikoko outlines these options for patients.
Xalkori (critzotinib) was the first approved treatment for ALK+ and ROS1 lung cancer. Since then, other drugs have been approved or are currently undergoing scientific review. In this video, Dr. Owonikoko outlines these options for patients.