Kelly Goodwin, MSN, RN, ANP-BC, discusses the significance of the recent FDA approvals of capmatinib and trastuzumab deruxtecan for patients with non–small cell lung cancer.
Last month, 2 targeted therapies were added to the fold of FDA approved non–small cell lung cancer (NSCLC) treatments. Capmatinib (Tabrecta) was approved for patients with metastatic disease whose tumors harbor a MET exon 14 skipping and fam-trastuzumab deruxtecan-nxki (Enhertu) was approved for previously treated patients with HER2-mutated unresectable or metastatic NSCLC.1,2
“For patients with metastatic NSCLC, the goal of systemic therapy is to live as well as possible for as long as possible,” Kelly Goodwin, MSN, RN, ANP-BC said. "A better understanding of the molecular pathways that contribute to NSCLC has led to the development of targeted therapies that have helped to improve survival rates and decrease treatment-related toxicities for certain subsets of patients with NSCLC.”
In an interview with Oncology Nursing News®, Goodwin, a nurse practitioner with the Mass General Cancer Center's Thoracic Oncology Team, highlighted how the approvals of these 2 targeted therapies are continuing to expand options for patients with NSCLC, and what nurses who are caring for these patients should know about their safety profiles.
Capmatinib for MET exon skipping 14 NSCLC
The regulatory decision to grant capmatinib full approval was supported from findings from the phase 3 GEOMETRY mono-1 trial (NCT02414139). Findings from this trial demonstrated that patients with MET exon 14 skipping mutations who received capmatinib experienced promising overall responses.1,3
“In GEOMETRY mono-1, patients with MET exon 14 skipping mutations and MET gene amplifications [who] received capmatinib [had] meaningful responses and an acceptable safety profile across all cohorts,” Goodwin said. “Patients who received capmatinib as the first line of therapy achieved a median OS [overall survival] of 20.8 months, overall response rate [ORR] of 67.9%, median duration of response [DOR] of 12.6 months, and a median progression-free survival [PFS] of 12.4 months. [In comparison, these patients achieved] an OS of 13.6 months, an ORR of 40.6%, a median DOR of 9.7 months, and a median PFS of 5.4 months if used in the second or third-line setting.”
According to Goodwin, this approval may be especially beneficial for patients who identify as nonsmokers.
“Research has shown that cancer promoting mutations can be found across all lung cancer histologies and smoking histories,” she said. “[However], MET exon 14 skipping mutations are more frequently identified in patients with nonsquamous tumor histology, older patients, and females who are less likely to be nonsmokers. MET exon 14 skipping mutations or MET gene amplifications are found in approximately 2% to 4% of NSCLCs through RNA based NGS [next-generation sequencing] testing.”
Approval of Tepotinib
Tepotinib (Tepmetko) is also approved for the same indication but, unlike capmatinib, has not been granted full approval. The accelerated approval was supported by findings from the phase 2 VISION trial (NCT02864992), which showed that patients with MET exon 14 skipping who received tepotinib achieved an ORR of 43% and a median DOR of 11.1 months (95% CI, 9.5-18.5).4 According to Goodwin, it is exciting to have 2 approved targeted therapies on the market for this subtype.
“Tepotinib received FDA approval for the treatment of metastatic NSCLC harboring a MET exon 14 skipping mutations less than 1 year after the approval of capmatinib—marking an exciting time for patients, caregivers and providers,” she said.
The 2 agents have demonstrated comparable efficacy thus far, although capmatinib may be preferred in the frontline.
“Overall response rates and DORs were similar across lines of therapy in patients in patients receiving tepotinib, [although] there appears to be a significant benefit to frontline capmatinib,” Goodwin said.
In terms of safety, the drugs are similar, she added. Although myalgias have been reported with tepotinib, overall, peripheral edema, gastrointestinal toxicity, fatigue, appetite changes, and dyspnea are common in patients treated with either MET inhibitor. Moreover, potentially life-threatening interstitial lung disease (ILD)/pneumonitis and transaminitis have been observed in patients treated with both agents.3,4
Goodwin noted that several factors can influence treatment recommendations, including factors such as functional status, symptom or disease burden, and pre-existing comorbidities. A patient’s ability or willingness to adhere to treatment, as well as their medication coverage with insurance, are factored into decision-making as well. In her own practice, she has noticed that capmatinib is being offered more consistently, however, she acknowledges that this agent has been available for longer.
“In my own practice I have seen capmatinib used more regularly and I think this is partly a reflection of the drug being first to market—providers look at efficacy, safety and cost closely when making a decision to integrate later approvals into the practice,” Goodwin said, noting that many of the patient education points are similar with the 2 MET inhibitors.
“Regardless of drug selection, it is important to ask patients to call immediately with sudden changes in their breathing including new or worsening shortness of breath, a persistent cough, chest tightness or wheezing, given the risk of ILD/pneumonitis,” she continued. “Patients should also be encouraged to call with poorly controlled nausea, vomiting or bowel changes associated with lightheadedness, weakness or weight loss, given the risk of renal dysfunction.”
Moreover, nurses and patients should be aware peripheral edema is a common adverse effect of MET inhibitors, meaning that patient should be encouraged to call if any asymmetric peripheral edema, calf pain, skin changes or fevers, as these may be indicative of greater venous thromboembolism risk. Similarly, patients who are receiving MET inhibitors benefit from multidisciplinary care. Goodwin recommended referring these patients to a nutritionist to optimize their care and proactively manage treatment-related edema risk.
The approval of trastuzumab deruxtecan marks the first HER2-directed targeted therapy available for patients with NSCLC.2 According to Goodwin, this approval is changing the dynamic of how patients with this disease are being treated.
“The approval of trastuzumab deruxtecan is revolutionary—bringing more effective, safer targeted therapies to a growing number of patients living with NSCLC,” she said. “With more comprehensive biomarker testing and safer, more effective, therapies our patients are living longer.”
This approval was supported by data from the phase 2 DESTINY-Lung02 (NCT04644237). The trial showed that patients with advanced HER2-mutant NSCLC derived durable clinical benefit from the antibody-drug conjugate.The median ORR was 57.7% (95% CI, 43.2%-71.3%); the median PFS was 8.2 months, and the median overall survival was 17.8 months. Data surrounding central nervous system (CNS) activity is not yet mature.5
“Many patients with metastatic lung cancer are found to have CNS metastasis at initial diagnosis or later in their treatment course,” Goodwin explained. “Review of the data DESTINY- Lung02 data indicates CNS responses with trastuzumab deruxtecan, but routine screening and surveillance was not required on study,” she added. “I am eager to see the final data around CNS activity and to see if there are differences in safety and efficacy in the 2 doses being studied.”
In terms of safety, no new signals were reported in the DESTINY-Lung02 trial. Yet, Goodwin still advises solid monitoring throughout a patient’s first few cycles.
“The drug is given IV [intravenously] every 3 weeks, but I encourage patients to be seen weekly during the first cycle or 2 of therapy for laboratory monitoring and symptom management,” she said. “As trastuzumab deruxtecan is approved in the second-line setting and beyond, patients may be experiencing more disease related symptoms at the time of treatment initiation and may have borderline bone marrow function.”
Moreover, trastuzumab deruxtecan carries boxed warnings for potentially fatal ILD, neutropenia, and left ventricular dysfunction.”
According to Goodwin, patients should be encouraged to call the office immediately for sudden respiratory changes including dyspnea, cough, wheezing, chest tightness or pain, fluid retention/weight gain or fevers/signs of infection.
“I recommend patients have a thermometer, scale, and pulse oximeter at home, if possible,” she said. “[In addition], all patients should undergo a baseline echocardiogram before starting therapy and every 3 months while on therapy or sooner as clinically indicated. If a patient has underlying cardiac disease, it is important to engage cardiology for any changes in clinical condition. Patients with respiratory changes should undergo in-person evaluation with resting and ambulatory oxygen saturation monitoring and high-resolution CT scans.”
Any dizziness or palpitations should be reported right away, she added.
She shared that dose delays and reductions, as well as the use of growth factors or blood products, can be employed help patients who are experiencing side effects related to therapy. However, patients who develop radiographic or symptomatic pneumonitis that is worse than grade 1 should not be rechallenged.