Chemotherapy Plus Immunotherapy Shows No Benefit Following Osimertinib in EGFR+ NSCLC

Treatment with chemotherapy plus immunotherapy did not demonstrate significant clinical benefit over chemotherapy alone in patients with EGFR-mutated non–small cell lung cancer (NSCLC) after progression on osimertinib (Tagrisso), according to data from a single-center, retrospective study presented during the 2021 European Lung Cancer Virtual Congress.

Results showed that the median overall survival (OS) for patients who received chemotherapy plus immunotherapy (n = 12) was 10.9 months (95% CI, 9.4–not estimable [NE]) compared with 10.6 months (95% CI, 6.9-19.5) for chemotherapy alone (n = 29). The duration on treatment (DOT) with the combination was 5.2 months (95% CI, 2.5–NE), and 3.9 months (95% CI, 1.9-7.8) for chemotherapy alone.

In patients who were treated with chemotherapy plus bevacizumab (Avastin; n = 34) the median OS was 13.9 months (95% CI, 10.2–NE), while the DOT was 5.8 months (95% CI, 4.5-11.7).

“Larger cohorts from multiple institutions, including those that use chemotherapy plus immunotherapy [or] plus bevacizumab in the immediate post-osimertinib setting, would be helpful to guide treatment decisions until randomized trial data are available,” Maya N. White, MD, of Stanford Cancer Institute, and coinvestigators wrote in a poster presenting the data.

After progression on osimertinib, platinum doublet chemotherapy-based regimens are the standard of care for patients with EGFR-mutant lung cancer. Previously, the combination of chemotherapy plus pembrolizumab (Keytruda) was examined in patients without EGFR or ALK mutations in the phase 3 KEYNOTE-189 trial (NCT02578680) and demonstrated an improvement in survival outcomes.

Additionally, the combination of chemotherapy and bevacizumab also showed a survival benefit in molecularly unselected patients with NSCLC in the phase 3 ECOG-4599 trial (NCT00021060). However, the efficacy of these treatment strategies for patients with EGFR mutations is unknown.

In the retrospective study, investigators sought to examine the outcomes of chemotherapy with or without immunotherapy, as well as chemotherapy plus bevacizumab, each compared with chemotherapy alone in patients with EGFR-mutant NSCLC. The primary end points included DOT and OS.

Patients enrolled had EGFR-positive NSCLC who had previously received osimertinib in the first-second, or third-line setting, and then went on to subsequently receive platinum doublet chemotherapy with or without immunotherapy or bevacizumab. Additionally, those who continued on osimertinib were eligible for enrollment. Patients who previously received chemotherapy, immunotherapy, or antiangiogenic agents in the metastatic setting, as well as those with biopsy-proven small cell transformation were excluded.

Enrollment began in July 2020, and the data cutoff date was February 9, 2021.

Of the 75 patients were enrolled and received platinum doublet chemotherapy-based regimens, 29 received chemotherapy alone, 12 received chemotherapy/immunotherapy, and 34 patients received chemotherapy/bevacizumab.

Across all cohorts, the median age was 60.7 years old, and the majority of patients were female (60%), Asian (52.3%), and had an ECOG performance status of 0 or 1 (83.3%).

In the chemotherapy-alone cohort, 48% of patients had EGFR exon 19 deletion mutations, while 48% had L858R mutations; 3% of patients had other. Also in this subgroup, 41% had received prior treatment with osimertinib up front, while 59% had received first-line treatment with other EGFR TKIs before going onto osimertinib.

Among patients in the chemotherapy/immunotherapy cohort, 58% had EGFR exon 19 deletion mutations and 42% had L858R mutations; 58% had received first-line treatment with osimertinib, and 42% received frontline treatment with other EGFR TKIs before osimertinib.

Finally, in the chemotherapy/bevacizumab cohort, 53% of patients had L858R mutations, and 44% had EGFR exon 19 deletion mutations. Thirty-eight percent had osimertinib up front, while 62% received first-line treatment with other EGFR TKIs before osimertinib.

Ongoing randomized trials examining outcomes in patients with EGFR-mutant NSCLC after progression on osimertinib include the phase 3 KEYNOTE-789 (NCT03515837), phase 3 CheckMate-722 (NCT02864251), and the phase 2 TH-138 (NCT03786692) trials.

Reference

White M, Neal J, Gardner R, et al. Chemotherapy with or without immunotherapy or chemotherapy plus bevacizumab versus chemotherapy alone in EGFR-mutated lung cancer after progression on osimertinib: a single center retrospective study. Presented at: 2021 European Lung Cancer Virtual Congress; March 25-27, 2021; virtual. Abstract 141P.