Dr Massarelli on Using of Selpercatinib and Pralsetinib in Treating Advanced Non-Small Cell Lung Cancer

Erminia Massarelli, MD, PhD, MS, co-director, Lung Cancer and Thoracic Oncology Program, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses considerations for the use of selpercatinib (Retevmo) or pralsetinib (Gavreto) in treating patients with advanced non–­small cell lung cancer (NSCLC) harboring 

Both selpercatinib and pralsetinib have been granted regular approval by the FDA for the treatment of adult patients with locally advanced or metastatic NSCLC harboring a RET gene fusion, as detected by an FDA-approved test. 

Massarelli notes that selpercatinib has demonstrated superiority over chemotherapy given with or without immunotherapy in the first-line treatment of patients with 

 fusion–positive NSCLC. Similarly, she explains that pralsetinib has shown efficacy in treating patients with advanced NSCLC harboring RET fusions, making it another valuable therapeutic option for this patient population.

Both selpercatinib and pralsetinib are utilized in clinical practice for the treatment of patients with advanced 

 fusion–positive NSCLC, Masserelli explains. These treatments offer patients a more targeted approach, providing a significant benefit over traditional chemotherapy regimens.

She explains that the safety profile of each agent should be considered when making a treatment decision for a patient with NSCLC harboring a 

 fusion. The toxicity profiles of selpercatinib and pralsetinib share similarities, including adverse effects (AEs) such as pneumonitis and hypertension. These AEs are typical of RET tyrosine kinase inhibitors (TKIs) and require careful monitoring and management, Massarelli notes. She adds that selpercatinib has also been associated with ascites, although Massarelli explains that this is uncommon. Massarelli mentions that the incidence and severity of AEs may increase with prolonged use of RET TKIs, necessitating ongoing vigilance.

The efficacy and safety profiles of these RET inhibitors underscore their importance in clinical practice, providing new avenues for managing this challenging patient population, Massarelli concludes.

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Erminia Massarelli, MD, PhD, MS, discusses selpercatinib and pralsetinib in treating advanced non-small cell lung cancer.

Dr Massarelli on Using Selpercatinib and Pralsetinib in Treating Advanced Non-Small Cell Lung Cancer

Erminia Massarelli, MD, PhD, MS, co-director, Lung Cancer and Thoracic Oncology Program, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses clinical gaps in lung cancer care that were highlighted at the 2023 Bridging the Gaps in Lung Cancer meeting, emphasizing the importance of molecular testing in patients with small cell lung cancer (SCLC) and collaborations between health care networks in this treatment arena.
At the 2023 Bridging the Gaps in Lung Cancer meeting, Massarelli chaired a session on SCLC where she expanded on the current treatment armamentarium for this patient subgroup. During this session, Massarelli and other presenters shed light on the current state of SCLC treatment and discussed potential novel treatment approaches for patients with SCLC.

A recurring theme underscored throughout each discussion was the need to treat each patient as a unique individual, she expands. Massarelli emphasizes the importance of understanding that there is not a one-size-fits-all approach for lung cancer. For example, the smoking status of a patient with SCLC holds substantial relevance in the therapeutic decision-making process, Massarelli explains.

Moreover, molecular testing is important, though not essential, in patients with a history of smoking, she continues. However, for patients with SCLC who have never smoked, these molecular tests are crucial. These tests are a critical tool for deciphering whether a transformative event has occurred within the patients’ disease progression, Massarelli says.

Furthermore, the conventional first-line treatment for patients with SCLC predominantly consists of chemotherapy and immunotherapy. However, following disease progression, enrolling patients in a clinical trial becomes a priority, she explains, because second- and third-line SCLC treatment approaches yield limited success rates. In light of these challenges, large oncology networks must collaborate. These combined efforts are pivotal in the pursuit of more effective SCLC treatments and better patient outcomes, Massarelli concludes.

Erminia Massarelli, MD, PhD, MS, discusses clinical gaps in lung cancer care that were highlighted at the 2023 Bridging the Gaps in Lung Cancer meeting, emphasizing the importance of molecular testing in patients with small cell lung cancer and collaborations between health care networks in this treatment arena.


Dr Massarelli on the Current SCLC Treatment Armamentarium

Erminia Massarelli, MD, PhD, MS, co-director, Lung Cancer and Thoracic Oncology Program, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses unmet needs in the treatment of patients with small cell lung cancer (SCLC) that were discussed at the 2023 Bridging the Gaps in Lung Cancer meeting, as well as how further research may help mitigate these needs.

One gap in care hindering advances in SCLC treatment is the lack of individually tailored research and therapies for the 2 main types of SCLC: SCLC in former or current smokers, and SCLC in never-smokers. The latter subtype usually arises as a transformation from a molecularly driven disease, such as 

-mutated non–small cell lung cancer, Massarelli says. These 2 categories of SCLC differ from each other, and thus require different testing and treatment considerations, Massarelli notes. Molecular testing is crucial in never-smokers with transformed SCLC, as it can reveal targetable drivers of disease, Massarelli emphasizes. Although molecular testing may also be useful in patients with smoker-driven SCLC, the advantages of identifying molecular drivers and potential targeted treatment options in this patient subset remain unclear, Massarelli explains.

Another important gap in the management of patients with SCLC is the lack of effective therapies in this population, according to Massarelli. The progress in this area over the past 30 years has been minimal, Massarelli says. One of the most recent FDA approvals of an immunotherapy for patients with SCLC was the 2019 

accelerated approval of pembrolizumab (Keytruda) monotherapy in patients with metastatic disease

 who had progressed on at least 2 prior lines of therapy, including 1 line of platinum-based chemotherapy. Several clinical trials led by academic institutions and pharmaceutical companies are ongoing to address the need for more SCLC treatment options, Massarelli notes. Patients with SCLC are encouraged to participate in these trials, which may lead to the discovery of novel targets and treatments, Massarelli concludes.

Erminia Massarelli, MD, PhD, MS, discusses unmet needs in the treatment of patients with small cell lung cancer that were discussed at the 2023 Bridging the Gaps in Lung Cancer meeting, as well as how further research may help mitigate these needs.

Dr Massarelli on Addressing Unmet Needs in SCLC

Erminia Massarelli, MD, PhD, MS, co-director, Lung Cancer and Thoracic Oncology Program, section chief, Thoracic Oncology, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses strategies created by City of Hope to effectively navigate the treatment of patients with lung cancer during the platinum chemotherapy shortage in the United States.

Of the 27 institutions in the United States 

polled by the National Comprehensive Cancer Network (NCCN) Best Practices Committee

 between May 23 and 31, 2023, 93% are experiencing a shortage of carboplatin, and 70% currently have a shortage of cisplatin. As a result, many institutions have enacted strategies to reduce the burden of this shortage and ensure patients are still able to receive adequate, necessary treatment.

Leaders at City of Hope aimed to prioritize the administration of their current platinum-based chemotherapy supply for patients in the curative setting, as well as those who did not have treatment alternatives, Massarelli states. This includes the majority of patients within the lung cancer space, specifically patients in the first line, Massarelli notes.

For the remaining patients, the institution was tasked with identifying effective and appropriate alternative regimens for treating their patients with cancer in the interim. One approach considered for patients with advanced lung cancer in the first line was the phase 3 CheckMate 9LA [NCT03215706] regimen of nivolumab (Opdivo) plus ipilimumab (Yervoy) combined with 2 cycles of platinum chemotherapy, Massarelli says. As this regimen includes less chemotherapy, it was an ideal approach to help conserve the current supply of platinum agents, while still remaining efficacious, Massarelli explains.

Ultimately, the majority of patients at City of Hope were able to be accommodated, Massarelli states. The success of these mitigation efforts has fortunately allowed City of Hope to lift the restrictions on platinum chemotherapy use, Massarelli concludes. However, the shortage continues to be a concern for many healthcare centers across the nation.

Erminia Massarelli MD, PhD, MS, discusses strategies created by City of Hope to effectively navigate the treatment of patients with lung cancer during the platinum chemotherapy shortage in the United States.

Dr Massarelli on Effectively Treating Patients During the United States Chemotherapy Shortage

Erminia Massarelli MD, PhD, MS, codirector, Lung Cancer and Thoracic Oncology Program, section chief, Thoracic Oncology, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses efficacy and safety data with the NTRK inhibitors larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) in patients with non–small cell lung cancer (NSCLC) harboring 

Approximately 0.2% of all patients with NSCLC cases have 

 fusion–positive disease, Massarelli says. There are currently 2 FDA-approved agents for this population: larotrectinib and entrectinib. 

 fusion–positive solid tumors. In 2019, 

entrectinib received accelerated approval

 for adult and pediatric patients at least 12 years of age with 

Both entrectinib and larotrectinib have elicited strong and durable responses in patients with NSCLC, and both have effective brain penetration, which is important as 40% to 50% of patients with 

 fusion–positive NSCLC can eventually develop brain metastases, Massarelli notes. Updated efficacy and safety data from an integrated analysis of the locally advanced or metastatic 

 fusion–positive NSCLC cohorts of the pivotal phase 1 ALKA-372-001 (EudraCT 2012-000148-88), phase 1 STARTRK-1 (NCT02097810), and phase 2 STARTRK-2 (NCT02568267) trials were presented at the 2023 ASCO Annual Meeting. In this analysis, entrectinib elicited an intracranial overall response rate of 60.0% (95% CI, 26.2%-87.8%). The median duration of response in patients with baseline central nervous system metastases was 29.4 months (range, 5.6-29.4). Additionally, the median duration of intracranial response was not evaluable (NE; 95% CI, 8.0 months-NE).

The safety profiles of entrectinib and larotrectinib are manageable, with few grade 3 treatment-related adverse effects (TRAEs) observed with either agent in their respective pivotal trials. Grade 3 TRAEs associated with larotrectinib include anemia and decreased white blood cell counts, and grade 1/2 TRAEs associated with entrectinib include dysgeusia, fatigue, and diarrhea, Massarelli explains. Patients who receive entrectinib may also experience weight gain or fluid retention, Massarelli concludes.

Erminia Massarelli MD, PhD, MS, discusses efficacy and safety data with the NTRK inhibitors larotrectinib and entrectinib in patients with non–small cell lung cancer harboring NTRK fusions.

Dr Massarelli on NTRK Inhibitors in NTRK Fusion+ NSCLC

Erminia Massarelli, MD, PhD, MS, co-director, Lung Cancer and Thoracic Oncology Program, section chief, Thoracic Oncology, associate professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses unmet needs in 

 exon 20–mutated non–small cell lung cancer (NSCLC).

Brain metastasis is difficult to treat in this patient population, as there is not clear data that EGFR exon 20 inhibitors are effective in patients with brain metastases, Massarelli explains. Current agents such as mobocertinib (Exkivity) do not penetrate the central nervous system (CNS), Massarelli says. Therefore, clinicians are awaiting data from a new class of compounds that may have the potential to penetrate the CNS.

The bispecific antibody, amivantamab-vmjw (Rybrevant), targets EGFR and MET, but still does not penetrate the blood brain barrier, Massarelli continues. There is still much to be desired in this area, as clinicians await a new class of drugs in clinical trials that will fulfill this unmet need, Massarelli concludes.

Erminia Massarelli, MD, PhD, MS, discusses unmet needs in EGFR exon 20–mutated non–small cell lung cancer.


Dr. Massarelli on Unmet Needs in EGFR Exon 20–Mutated NSCLC

Erminia Massarelli, MD, PhD, MS, co-director of the Lung Cancer and Thoracic Oncology Program, section chief of Thoracic Oncology, and associate professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, discusses advances in frontline immunotherapy in non–small cell lung cancer (NSCLC).

Many novel immunotherapy combinations are emerging, such as those combining anti-TIGIT antibodies and LAG-3 inhibitors, Massarelli says. One combination currently being studied is that of an anti-TIGIT antibody and checkpoint inhibitor, which has shown promise in patients with PD-L1 levels of 50% or higher, Massarelli explains.

Other clinical trials studying immunotherapy include those looking at cell therapy in NSCLC, Massarelli notes. Combinations of immuno-oncology molecules with TKIs such as lenvatinib (Lenvima) are also promising, Massarelli concludes.

Erminia Massarelli, MD, PhD, MS, discusses advances in front-line immunotherapy in non–small cell lung cancer.

Erminia Massarelli, MD, PhD, MS

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