Excellent Response to Gefitinib in a Patient with Erlotinib Refractory, Exon 21, L858r Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma

Sir,

A 61-year-old man, a nonsmoker, presented to our hospital with a right lung mass and right-sided, rapidly refilling, massive pleural effusion with multiple, bilateral lung, liver, and bone metastases.

Bronchoscopic biopsy revealed adenocarcinoma of the lung. He was started on pemetrexed and carboplatin every 3 weeks. The epidermal growth factor receptor (EGFR) mutation analysis done by polymerase chain reaction technique revealed an exon 21, L858R (an arginine for leucine substitution at amino acid 858) mutation.

He had an excellent clinical response to the first cycle of chemotherapy and was thus given six cycles followed by 4 weekly maintenance with single-agent pemetrexed. After the third cycle of maintenance, he developed progressive disease which was confirmed by an 18-fluorodeoxyglucose positron emission tomography (PET) scan. He was started on erlotinib 150 mg/day to which there was no response. The PET scan done at 8 weeks was suggestive of progressive disease [Figure 1]a with a heterogeneously enhancing mass lesion 7.9 cm × 5.5 cm × 7.5 cm (previously 5.9 cm × 4.6 cm × 7 cm) in the right suprahilar region, pulmonary parenchymal, mediastinal lymph nodal, and solitary skeletal metastases and right pleural effusion. The patient was not receiving any medications that might change the serum levels of the EGFR inhibitors, such as CYP3A4 inducers or inhibitors.{Figure 1}

Figure 1: (a) Left-sided images showing positron emission tomography scan revealing right suprahilar mass lesion with pulmonary parenchymal involvement after erlotinib therapy and before the start of gefitinib. (b) Right-sided images showing positron emission tomography scan done 3 months after institution of gefitinib showing partial response

He was started on gefitinib 250 mg a day. Within 2 weeks, he reported significant clinical improvement. A PET scan done 3 months later revealed partial response with marked resolution of the lung lesions [Figure 1]b. The patient exhibited excellent radiological and clinical response to the drug. The response lasted for 14 months when unfortunately the disease progressed. He died 3 months later after disease progression (no additional mutation or T790 mutation detected on repeat biopsy) after failing to respond to afatinib and nivolumab as salvage therapies.

Publication History

Article published online:
17 June 2021

• References

• 1 Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C. et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12: 735-42
• 2 Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I. et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004; 101: 13306-11
• 3 Chen YR, Fu YN, Lin CH, Yang ST, Hu SF, Chen YT. et al. Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants. Oncogene 2006; 25: 1205-15
• 4 Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M. et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: Mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 2007; 11: 217-27
• 5 Choong NW, Dietrich S, Seiwert TY, Tretiakova MS, Nallasura V, Davies GC. et al. Gefitinib response of erlotinib-refractory lung cancer involving meninges – Role of EGFR mutation. Nat Clin Pract Oncol 2006; 3: 50-7