How EGFR and PD-1 Pathway Agents May Change Lung Cancer Care

Tara Petersen
Published: Thursday, Sep 17, 2015
Dr. Mark Socinski

Mark Socinski, MD

As new targeted and immunologic agents are introduced for patients with lung cancer, clinicians have more factors to consider than ever before when developing treatment plans for their patients. In an effort to help shed light on the latest research, leading experts in the field shared their thoughts on how the new data might influence current practices during a recent OncLive Peer Exchange program.

The panelists discussed data presented at the 2015 ASCO Annual Meeting including findings for small cell lung cancer (SCLC), which historically has had few therapeutic options.

“Modern treatment of advanced lung cancer is based on tumor histology and molecular subtype, with new advances in the field happening at an accelerated pace,” noted moderator Mark A. Socinski, MD, as he launched a wide-ranging discussion.

EGFR-Targeting Therapies

Incorporating Gefitinib

With the approval of Iressa (gefitinib) in July, oncologists have one more epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in their armamentarium. In 2003, gefitinib became the first EGFR inhibitor approved for patients with non–small cell lung cancer (NSCLC), but the product was withdrawn after postmarketing studies failed to confirm a clinical benefit.

Since that time, data among patients with known mutation status have shown there is a benefit in EGFR-positive disease. The latest approval is for first line use in patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 substitution mutations.

Mary Jo Fidler, MD

Mary Jo Fidler, MD

One interesting point about the phase IV data from the IRESSA Follow Up Measure (IFUM) study,1 noted Mary Jo Fidler, MD, is the use of serum samples in mutation testing. At baseline, one tissue and two plasma samples were collected for EGFR mutation analysis. A comparison of baseline tumor and plasma EGFR mutation status was part of the preplanned analyses. The results showed a high concordance (94.3%) between samples.1

“Though tissue certainly is more sensitive, the trial showed that you can, in fact, detect the EGFR gene activating mutation in serum, which I thought was pretty exciting,” remarked Fidler.

The panel discussed how they would incorporate gefitinib into treatment regimens, given the availability of two other EGFR inhibitors, erlotinib and afatinib, for treatment in this population. Roy S. Herbst, MD, PhD, noted that there are many similarities between erlotinib and gefitinib.

However, one of the differentiating factors is the dosing. With erlotinib, the recommended starting dose is 150 mg, and that is usually reduced. By contrast, gefitinib is given as a fixed dose at 250 mg.

Roy Herbst, MD

Roy Herbst, MD

Geoffrey R. Oxnard, MD, echoed this assessment, noting that the fixed dose could be seen as an advantage. “Some [physicians] like gefitinib because it’s flat dosing. You don’t have to dose adjust,” said Oxnard. He added that, although erlotinib offers flexibility with dosing, “it’s a little more work to find the right dose for the patient.”

Third-Generation Inhibitors

The panel discussion turned to the topic of acquired resistance, a common occurrence in patients treated with targeted agents that presents significant treatment challenges.

There are promising new data in patients whose tumors develop the EGFR T790M mutation, the dominant mutation pattern observed in EGFR-positive NSCLC.

Third generation TKIs, rociletinib (CO-1686) and osimertinib (AZD9291), target sensitizing mutations, but do not target wild-type EGFR. Thus, there is less rash and diarrhea associated with these agents compared with first- and second- generation drugs that have greater potency toward wild-type EGFR, noted Oxnard.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Provider and Caregiver Connection™: Addressing Patient Concerns While Managing Chemotherapy Induced Nausea and VomitingOct 31, 20182.0
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