View recent research presentations given by Mass General Cancer Center thoracic oncology team members.
2019 ASCO Annual Meeting
The 2019 ASCO (American Society of Clinical Oncology) Annual Meeting was held in Chicago, Illinois, on May 31st through June 4th 2019. The Mass General Thoracic Oncology Program was represented in several research presentations and abstract posters, including the following:
Justin Gainor, MD
Justin Gainor, MD, presented an oral abstract on, “Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC).” His presentation was featured in the ASCO Daily News. Dr. Gainor also gave an education session on The Evolution of ALK Small Molecules.
Alice Shaw, MD, PhD
Alice Shaw, MD, PhD, was the presenter for her poster entitled, “Early circulating tumor (ct)DNA dynamics and efficacy of lorlatinib in patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC).” She was a speaker in the poster discussion session focusing on plasma testing.
Lecia Sequist, MD, MPH
Lecia Sequist, MD, MPH, presented on What’s new with Therapies for EGFR-Sensitive Mutations during an education session. Dr. Sequist also presented a poster for her abstract, “SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC)."
Rebecca Heist, MD
Rebecca Heist, MD, presented a poster on, “c-Met expression and response to telisotuzumab vedotin (teliso-v) in patients with non-small cell lung cancer.” Her poster was selected for poster discussion session on "Old Targets, New Approaches,” during which she participated as a panelist.
Ibiayi Dagogo-Jack, MD
Ibiayi Dagogo-Jack, MD, presented a poster on, “Longitudinal analysis of plasma ALK mutations during treatment with next-generation ALK inhibitors.”
Anna Farago, MD, PhD
Anna Farago, MD, PhD, served as a discussant on two oral abstracts, and gave her talk on Relapsed SCLC: New Cytotoxic Strategies.
Jessica Lin, MD
Jessica Lin, MD, presented a poster titled, “Efficacy of platinum-pemetrexed combination chemotherapy in ALK+ non-small cell lung cancer refractory to second-generation ALK TKIs.”
Zosia Piotrowska, MD
Zosia Piotrowska, MD, presented her poster entitled, “Clinical outcomes of EGFR+ NSCLC pts treated with immune checkpoint inhibitors (ICI).”
2019 AACR Annual Meeting
The 2019 AACR Annual Meeting was held in Atlanta, Georgia, on March 29th through April 3rd 2019. The Mass General Thoracic Oncology Program was represented in several research presentations, including the following:
- Alice Shaw, MD, PhD, presented on “Refining Precision Medicine in Non-Small Cell Lung Cancer”. Dr. Shaw reviewed the general landscape of targeted therapies in advanced lung cancer and focused on the latest discoveries in ALK-rearranged lung cancer. Her presentation highlighted the rapid translation of basic research findings into the clinic in the form of novel therapies and combination strategies. Dr. Shaw also presented at the Meet the Expert Session on Lung Cancer Trials.
- Justin Gainor, MD, presented on behalf of the SU2C/ACS Lung Cancer Dream Team, entitled “Identifying determinants of response to immune checkpoint blockade in non-small cell lung cancer.” In the last several years, immunotherapy has transformed the management of NSCLC, but a majority of patients do not respond to therapy. The SU2C Lung Cancer Dream Team has launched a major collaborative research effort to explore genomic, pathologic and clinical factors associated with response and resistance to checkpoint inhibitors. In this talk, Dr. Gainor summarizes the progress to date.
- Lecia Sequist, MD, MPH, presented on “TATTON phase Ib expansion cohort: Osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior first/second generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI),” and on “TATTON phase Ib expansion cohort: Osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)”. To date, targeted therapy for lung cancer patients with EGFR mutations has consisted solely of monotherapy with various EGFR tyrosine kinase inhibitors (TKIs), though we have known for more than 10 years that a proportion of resistance to EGFR TKIs results from activation of the MET bypass pathway. Prior research has shown that MET amplification is a bypass pathway observed in about 5-10% of patients whose disease has progressed after treatment with first- or second-generation EGFR TKIs and in about 25% of those whose disease has progressed after treatment with third-generation EGFR TKIs. Data from the TATTON trial demonstrate for the first time the benefit of adding a MET inhibitor to an EGFR inhibitor in patients with EGFR-mutant NSCLC and with MET-driven acquired resistance. The study has shown efficacy of combination targeted therapy in a patient population for whom chemotherapy is the current primary treatment option. These clinically meaningful responses also demonstrate that as different heterogeneous resistance clones come up, they can in turn be brought under control by tailoring therapy. Watch Dr. Sequist’s presentation (please play the following video starting at minute 33:00).
- Anna Farago, MD, PhD, presented on “Expansion of Phase I/II study of olaparib and temozolomide in patients with relapsed small cell lung cancer (SCLC) and co-clinical trial in patient-derived xenografts (PDXs) for biomarker discovery”. Dr. Farago present clinical data from a phase I/II trial of combination olaparib and temozolomide in patients with relapsed small cell lung cancer (SCLC), which demonstrate encouraging clinical activity of this combination in 50 patients treat in this study, supporting further clinical development of this strategy. In conjunction, they present a co-clinical trial testing the activity of olaparib and temozolomide in patient derived xenograft models of SCLC, and apply these models to discover novel candidate biomarkers of sensitivity and resistance. In another abstract, Dr. Farago presented on “Dose optimization of olaparib plus temozolomide in small cell lung cancer (SCLC) patient-derived xenograft (PDX) models for clinical translation”. Here Drapkin et al. present preclinical data designed to optimize the dosing strategy of combination olaparib and temozolomide in patients with relapsed small cell lung cancer. To do so, they apply patient-derived xenograft models. They conclude that dosing with continuous olaparib and intermittent temozolomide allows dose reductions of these therapies without compromising efficacy. These data lay important groundwork for the optimal clinical development of olaparib and temozolomide in patients. Dr. Farago also presented an abstract on “Combined inhibition of Bcl-2 and MCL-1 in small cell lung cancer (SCLC) is most effective in tumors with low Bcl-xL expression”. Here Drapkin et al. explore a new treatment strategy in small cell lung cancer (SCLC) using combined inhibition of Bcl-2 and MCL-1. In patient-derived xenograft models, they find that this combination is most effective in SCLC tumors with low expression of Bcl-xL. These data lay the groundwork for further clinical development of this combination.
Improving Outcomes for Patients with Non–Small Cell Lung Cancer
A Six-Part Virtual Tumor Board Integrating Best Practices and Emerging Evidence to Enhance Care
For over a decade, the treatment landscape of non–small cell lung cancer (NSCLC) has been rapidly evolving. It now includes testing for genetic alterations and the use of targeted therapies and immunotherapies, with new targets and treatments still being discovered and approved. In this six-part virtual tumor board, Dr. Alice Shaw, Dr. Lecia Sequist, Dr. Justin Gainor, discuss the newest diagnostic and therapeutic paradigms in the field of NSCLC using real-life case studies and highlight how employing these treatments may lead to improved outcomes for patients. Module topics include biomarker evaluation, targeted therapies for ALK-positive disease, combination chemotherapy and immunotherapy, and management of checkpoint inhibitor–associated immune-related adverse events.
- Module 1: Strategies for Biomarker Evaluation in Patients With NSCLC: From EGFR to PD-L1
- Module 2: Management of Locally Advanced NSCLC
- Module 3: Optimizing Selection of First-Line and Subsequent Treatment for Patients With Metastatic NSCLC
- Module 4: Treatment and Management of ALK-Positive NSCLC
- Module 5: Combining Cytotoxic Chemotherapy and Immunotherapy for Patients With NSCLC
- Module 6: Management of Immune-Related Adverse Events Associated With Checkpoint Inhibition
2018 World Lung Conference
The International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer took place in Toronto, Canada during September 23-26, 2018.
- Jessica Lin, MD, presented on the Safety and Preliminary Clinical Activity of Repotrectinib (TPX-0005), a ROS1/TRK/ALK Inhibitor, in Advanced ROS1 Fusion-Positive NSCLC. Repotrectinib demonstrated promising preliminary efficacy in ROS1 TKI-naive and ROS1 TKI -pretreated ROS1+ NSCLC. Activity was also observed in the central nervous system.
- Alice Shaw, MD, PhD, presented an ongoing global study of First-Line Lorlatinib Versus Crizotinib for Advanced Anaplastic Lymphoma Kinase-Positive (ALK+) Non Small Cell Lung Cancer. In this presentation, she described the study objectives, the study design, and the study treatments. To date, 66% of the patients have been accrued. This study will establish a role for lorlatinib as first-line therapy in advanced ALK-positive lung cancer. Dr. Shaw also presented at a symposium on Navigating the Spectrum of Resistance Mutations in ALK+ NSCLC: How to Identify and Treat Them. In this talk, Dr. Shaw described resistance mechanisms to first, second and third generation ALK inhibitors, with a special focus on secondary ALK kinase domain mutations. Dr. Shaw showed preclinical and clinical data supporting the utility of repeat biopsies after failure on a next generation ALK inhibitor to inform the selection of subsequent therapies. The third generation inhibitor lorlatinib can overcome all known single ALK resistance mutations, but loses activity against compound (double or triple) ALK mutations. New strategies and therapies are needed for patients who develop refractory compound ALK mutations.
- Anna Farago, MD, PhD, presented on Dynamics of DLL3 and ASCL1 Expression in SCLC Over Disease Course. Using patient biopsy samples and tissue from patient-derived xenograft models, Dr. Farago and colleagues showed that expression of DLL3 in small cell lung cancers remains mostly stable over time, despite intervening lines of therapy over multiple points. This result has important implications for drugs like Rovalpituzumab tesirine that target DLL3. In addition, Dr. Farago presented on Rapid, Robust and Durable Responses to Larotrectinib in Patients with TRK Fusion Non-Small Cell Lung Cancer. NTRK gene rearrangements in non-small cell lung cancer are rare events, occurring in approximately 0.2% of patients. However, Dr. Farago and colleagues showed that these tumors are highly sensitive to the TRK inhibitor larotrectinib, indicating that NTRK gene rearrangements are a targetable and important molecular subset of NSCLCs.
- Ibiayi Dagogo-Jack, MD, presented on Clinical Utility of Detecting ROS1 Genetic Alterations in Plasma. Dr. Dagogo-Jack collaborated with the scientific team at Guardant Health to analyze plasma specimens from approximately 60 patients with ROS1+ lung cancer. The study demonstrated the feasibility of detecting a variety of ROS1 fusions in plasma. In addition, Dr. Dagogo-Jack studied plasma specimens from a cohort of 16 patients relapsing on crizotinib and found that approximately 40% contained acquired ROS1 tyrosine kinase domain mutations, a finding similar to what has been demonstrated from analyzing tissue specimens at resistance. This is the largest plasma study of ROS1+ NSCLC to date and provides preliminary rationale for incorporating plasma genotyping into clinical management of ROS1+ NSCLC.
- Lecia Sequist, MD, participated in an academic debate about the use of Adjuvant Targeted Therapy for patients with Genomic Alterations. She also presented a poster with follow-up results from a Randomized Phase 2 Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer. This trial was a negative trial for the whole group of patients, though suggested that NSCLC patients with heregulin-expressing tumors might do well with seribantumab combinations. This concept is being further tested in an ongoing phase 2 trial called SHERLOC: A Phase 2 Study of Seribantumab in Combination with Docetaxel in Patients with Heregulin Positive, Advanced NSCLC.
- Meghan Mooradian, MD, presented on Immune-Related Adverse Events: The Growing Pains of Immunooncology. This work evaluated the spectrum of immune-related side effects that affected thoracic oncology patients and required hospitalization. Through her work, Dr. Mooradian hopes to advance the understanding of these toxicities in order improve detection and treatment of these events.
- Zofia Piotrowska presented on Activity of Osimertinib and the Selective RET Inhibitor BLU-667 in an EGFRMutant Patient with Acquired RET Rearrangement. She also served as a discussant for the presentation: Oncogene-Driven Patient Groups: A New Era for Research Partnerships.
- Rebecca Heist, MD, served as a discussant on Distinct Origins of Lymphatic and Brain Metastasis in Lung Cancer.
- Mari Mino-Kenudson, MD, presented on the Utility of PD-L1/CD8 Dual Immunohistochemistry for Prediction of Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC). Dr. Mino-Kenudson also presented on Laboratory Developed Test – CON.
2018 ASCO Annual Meeting
- Jennifer Temel, MD, gave an Education Session on the topic of “Exceptional responders, hope, and prognostication: making a tough problem even tougher.” She discussed how to communicate effectively with patients and their families about the goals and possible risks and benefits of patients’ cancer treatment to ensure they are prepared for all of the possible outcomes of therapy.
- Anna Farago, MD, PhD, Poster on "Safety and efficacy of combination olaparib and temozolomide in small cell lung cancer”, and on “ATLANTIS: global, randomized phase III study of lurbinectedin with doxorubicin vs. CAV or topotecan in small-cell lung cancer after platinum therapy.”
- Olaparib/ temozolomide: Dr. Farago presented data from a trial she is leading at MGH in which patients with relapsed small cell lung cancer are treated with a novel combination therapy approach using two drugs, olaparib and temozolomide. This phase 1/2 study is showing promising results, with approximately 40% of patients responding to treatment. Dr. Farago is continuing to expand this clinical trial, and is also performing parallel lab-based experiments to identify biomarkers for patients most likely to respond to this treatment. Watch the video.
- Lurbinectedin/doxorubicin: Dr. Farago is leading the global phase 3 randomized trial comparing an experimental therapy, lurbinectedin plus doxorubicin, to standard of care therapy for patients with relapsed small cell lung cancer. This clinical trial is currently enrolling patients and results are anticipated in the next 1-2 years.
- Lecia Sequist, MD, presented a poster on “The ASCENT trial: a phase II study of neoadjuvant afatinib, chemoradiation and surgery for stage III EGFR mutation-positive NSCLC,” and served as a discussant of abstracts on the topic of “Angiogenesis plus EGFR TKI: is progression-free survival enough?” The ASCENT trial was a pilot trial looking at adding targeted therapy to the standard of care for stage III lung cancer, a tri-modality approach h which means chemotherapy, radiation and surgery. Specifically recruiting patients with EGFR mutation, the trial started patients with 2 months of induction EGFR-targeted therapy (afatinib) and then transitioned them to tri-modality therapy. Dr. Sequist found that patients had high response rates, with 86% of patients having a major pathologic response on pathology at the time of surgery (< 5% viable tumor cells seen). The safety of this approach was good and no patients were unable to have their planned surgery because of induction afatinib. The trial continues to recruit more patients currently.
- Ibiayi Dagogo-Jack, MD, presented posters on “BRAF-mutant non-small cell lung cancer (NSCLC): patient (pt) characteristics and outcomes by class of mutation” and “clinicopathologic characteristics and molecular features of BRG1-deficient non-small cell lung cancer (NSCLC).”
- Justin Gainor, MD, gave a Clinical Science Symposium presentation on the “Response and durability of anti-PD-(L)1 therapy in never- or light-smokers with non-small cell lung cancer (NSCLC) and high PD-L1 expression.”
- Jessica Lin, MD, presented a poster on “Long-term efficacy and outcomes with sequential crizotinib followed by alectinib in ALK+ NSCLC.”
- Alice Shaw, MD, PhD, presented on “Avelumab (anti-PD-L1) in combination with crizotinib or lorlatinib in patients with previously treated advanced NSCLC: phase 1b results from JAVELIN Lung 101” during a Clinical Science Symposium session.
2018 AACR Annual Meeting
- Justin Gainor, MD, served as the discussant for the clinical plenary session, “IMpower150: PFS results for atezolizumab plus bevacizumab and chemotherapy across PD-L1 expression subgroups defined by the SP142 and SP263 IHC assays confirm all-comer benefit in 1L metastatic NSCLC.” IMpower150 was a large, well-conducted trial demonstrating that the addition of atezolizumab to carboplatin/paclitaxel and bevacizumab resulted in improved progression free survival, including across all PD-L1 subgroups. IMpower150 is the first randomized study to demonstrate significant benefit with checkpoint blockade among EGFR+/ALK+ patients.
- Alice Shaw, MD, PhD, gave a clinical trials plenary session presentation, entitled “Efficacy of lorlatinib in patients with advanced ALK -positive non-small cell lung cancer (NSCLC) and ALK kinase domain mutations”. She also served as a panelist in the discussion of “Precision Therapy: When Is Better—Up Front or at Relapse?”. In addition, she chaired and opened the plenary session entitled “Immunotherapy Combinations: The New Frontier in Lung Cancer”. Lorlatinib is a third-generation, highly potent and CNS penetrant ALK/ROS1 tyrosine kinase inhibitor with antitumor activity in ALK-positive advanced NSCLC. In patients who received crizotinib as their only prior ALK targeted therapy, treatment with lorlatinib led to responses regardless of ALK mutation status in patients. In patients previously treated with one or more second-generation ALK targeted therapy, a higher proportion of patients with an ALK mutation responded to treatment with lorlatinib compared to those without ALK mutations (26% vs 61%). In patients relapsing on a second-generation ALK inhibitor, ALK mutations may serve as a biomarker to identify patients more likely to respond to lorlatinib.