382MO - The preliminary safety result of a phase II study of osimertinib in combination with platinum + pemetrexed in patients with previously untreated EGFR-mutated advanced NSCLC (NEJ032C/LOGIK1801: OPAL)

Background

Based on the result of the FLAURA trial, osimertinib (OSI) is a standard of care in patients (pts) with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). One of the promising strategies to further improve pts' outcome is a combination therapy with OSI and platinum-doublet chemotherapy.

Methods

An ongoing multicenter phase II study is assessing the safety and efficacy of OSI + cisplatin (CDDP)/carboplatin (CBDCA) + pemetrexed (PEM) in previously untreated pts with EGFR-mutated NSCLC. A total of 67 pts were enrolled in arm A (CDDP) or arm B (CBDCA) at the discretion of each investigator. In addition to OSI 80 mg administered orally daily, CDDP (75 mg/m2)/CBDCA (AUC=5) and PEM (500 mg/m2) were administered intravenously every 3 weeks for up to 4 cycles. Pts without disease progression (PD) after 4 cycles of induction therapy continued OSI + PEM until PD or unacceptable toxicity. The co-primary endpoints are safety and objective response rate, and the secondary endpoints include complete response rate, disease control rate, and progression-free survival.

Results

As of 25 Feb 2020, 67 pts (34 in arm A; 33 in arm B) were enrolled: (median age 67 [range, 26-75] years; 43 female [64.2%]; 46 ECOG PS 0 [68.7%]; 66 adenocarcinoma [98.5%]; 31 EGFR ex19del [46.3%], 35 ex21 L858R [52.2%], 1 both [1.5%]). At the data cut-off (31 Mar 2020), 11 pts (16.4%) discontinued treatment: 2 (3.0%) due to PD; 6 (9.0%) adverse event (AE); 3 (4.5%) pts’ withdraw. At least one dose reduction was required in 41.2% (arm A) and in 57.6% (arm B). Most common (>5%) Grade 3≥ AEs were neutropenia (37.3%), lymphocyte count decreased (29.9%), white blood cell decreased (25.4%), platelet count decreased (19.4%), anemia (17.9%), anorexia (7.5%) and alanine aminotransferase increased (6.0%). One patient in arm B experienced grade 4 QT prolongation and terminated protocol treatment.

Conclusions

This is the first study to explore the efficacy and safety of OSI in combination with platinum-based chemotherapy as the first line treatment. This combination treatment has been well tolerated and follow-up is ongoing.

Clinical trial identification

jRCTs031180226.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

H. Asahina: Honoraria (self): AstraZeneca; Chugai; Kyowa Hakko Kirin. K. Tanaka: Honoraria (self): AstraZeneca; Eli Lilly; Advisory/Consultancy: AstraZeneca; Eli Lilly; Research grant/Funding (institution): AstraZeneca; Eli Lilly. S. Sugawara: Honoraria (self): AstraZeneca; Eli Lilly. R. Ko: Honoraria (self): Boehringer Ingelheim; Taiho Pharmaceutical; Chugai Pharmaceutical; Ono Pharmaceutical; Pfizer; AstraZeneca; Research grant/Funding (institution): Boehringer Ingelheim. S. Morita: Honoraria (self): AstraZeneca K.K.; Bristol-Myers Squibb Company; Chugai Pharmaceutical Co. Ltd.; Eli Lilly Japan K.K.; MSD K.K.; Nippon Boehringer Ingelheim Co. Ltd.; Ono Pharmaceutical Co. Ltd.; Pfizer Japan Inc.; Taiho Pharmaceutical Co. Ltd. M. Maemondo: Honoraria (self): AstraZeneca; Eli Lilly. M. Seike: Honoraria (self): AstraZeneca; Research grant/Funding (institution): Eli Lilly Japan. O. Isamu: Honoraria (self): AstraZeneca; Eli Lilly; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eli Lilly. K. Sugio: Research grant/Funding (institution): MSD. K. Kobayashi: Speaker Bureau/Expert testimony: AstraZeneca; Bristol-Myers Squibb Japan; Ono Pharmaceutical; Taiho Pharmaceutical Company. All other authors have declared no conflicts of interest.