Zofia Piotrowska, MD, MHS, a medical oncologist at Massachusetts General Hospital and an instructor at Harvard Medical School, discusses the utility of mobocertinib (formerly TAK-788) in patients with non–small cell lung cancer (NSCLC) who harbor 

Mobocertinib is an oral TKI that has demonstrated significant efficacy among patients with NSCLC and 

 exon 20 insertion mutations, says Piotrowska. During the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer, findings from a phase 1/2 study of mobocertinib in this patient population were presented and revealed an objective response rate of 26% per an independent review committee and 35% per investigator assessment. The median progression-free survival was 7.3 months. 

Although these results are encouraging, toxicity remains a concern with mobocertinib, as well as other emerging targeted therapies for this subset of patients, Piotrowska says. In the study, 90% of patients reported diarrhea and 45% reported rash as treatment-related adverse effects. Moreover, 21% of patients experienced grade 3 or higher diarrhea. As such, improvements in symptom management or development of novel therapies that are less toxic are needed, concludes Piotrowska. 

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Zofia Piotrowska, MD, MHS, discusses the utility of mobocertinib in patients with non–small cell lung cancer who harbor EGFR exon 20 insertions.  



Dr. Piotrowska on the Utility of Mobocertinib in EGFR Exon 20–Mutant NSCLC 

Zofia Piotrowska, MD, MHS, a medical oncologist at Massachusetts General Hospital and an instructor at Harvard Medical School, discusses the patient populations eligible to receive osimertinib (Tagrisso) as treatment for lung cancer.

The results of the FLAURA trial led to Piotrowska giving frontline osimertinib to patients with 

 exon 19 deletion, L858R, and other sensitizing mutations. When the trial was first published, there was a debate regarding whether it was beneficial to give patients erlotinib or gefitinib upfront. If the patient developed a T790M mutation, that left osimertinib as an option for second-line therapy; however, only about 60% to 70% of patients will develop T7090M. On the other hand, if osimitertinib is given upfront, patients will benefit for ≥19 months. When using the mentality that the best drug should be given upfront, osimertinib should be the frontline treatment according to the FLAURA data, says Piotrowska.

Second-generation EGFR inhibitors are considered for patients with uncommon but still sensitizing EGFR mutations. Afatinib (Gilotrif) is the only FDA-approved therapy for those mutations currently. Data for using osimiertinib on patients with G719, S768I, and other mutations are still being developed, but osimertinib may be used for those patients, as well, concludes Piotrwoska.

Zofia Piotrowska, MD, MHS, discusses the patient populations eligible to receive osimertinib as treatment for lung cancer.

Dr. Piotrowska on Eligibility Criteria for Osimertinib in Lung Cancer Treatment

Zofia Piotrowska, MD, MHS, a medical oncologist at Massachusetts General Hospital and an instructor at Harvard Medical School, discusses treatment strategies for 

-mutant non—small cell lung cancer (NSCLC).

The randomized phase III FLAURA trial, which compared osimertinib (Tagrisso) with erlotinib (Tarceva) and gefitinib (Iressa), showed that osimertinib improved progression-free survival and overall survival compared with the first-generation EGFR drugs in patients with metastatic 

-mutant NSCLC. The FLAURA trial establishes osimertinib as a standard of care for newly diagnosed 

-mutant patients with NSCLC, according to Piotrowska.

Aside from monotherapy, some combination treatments have potential to become a standard of care, including the combination of EGFR inhibitors with VEGF-targeted therapies or with chemotherapy, says Piotrowska. Both of these strategies have shown promise when combined with first-generation EGFR inhibitors, according to Piotrowska, and upcoming trials will look at combinations with osimertinib.

Piotrowska says it is important to identify 

-mutant patients early because, even if they have high PD-L1 expression, EGFR inhibitors are the standard treatment. There is risk to starting immunotherapy prior to receiving the results of the 

 test, because immunotherapy is not an effective treatment for patients with this molecular driver. Additionally, the risks of an EGFR inhibitor can be increased if started after immunotherapy. Therefore, the results of the 

 test must be received before starting treatment to give 

-mutant patients the appropriate TKI, concludes Piotrowska.

Zofia Piotrowska, MD, MHS, discusses treatment strategies for EGFR-mutant non–small cell lung cancer.

Zofia Piotrowska, MD, MHS

Articles

Dr. Piotrowska on the Utility of Mobocertinib in EGFR Exon 20–Mutant NSCLC

Dr. Piotrowska on Eligibility Criteria for Osimertinib in Lung Cancer Treatment

Dr. Piotrowska on Treatment for EGFR-Mutant NSCLC