Binimetinib, pemetrexed and cisplatin, followed by maintenance of binimetinib and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) and KRAS mutations. The phase 1B SAKK 19/16 trial.

Froesch, Patrizia; Mark, Michael; Rothschild, Sacha I; Li, Qiyu; Godar, Gilles; Rusterholz, Corinne; Oppliger Leibundgut, Elisabeth; Schmid, Sabine; Colombo, Ilaria; Metaxas, Yannis; König, David; Sessa, Cristiana; Gautschi, Oliver; Früh, Martin (2021). Binimetinib, pemetrexed and cisplatin, followed by maintenance of binimetinib and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) and KRAS mutations. The phase 1B SAKK 19/16 trial. Lung cancer, 156, pp. 91-99. Elsevier 10.1016/j.lungcan.2021.04.002

[img] Text
1-s2.0-S0169500221001318-main.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

BACKGROUND

KRAS mutations are found in 20-25 % of non-squamous non-small cell lung cancer (NSCLC) and therapies targeting the RAS/MEK/ERK pathway are in development. We performed a multicenter open-label phase 1B trial to determine the recommended phase 2 dose and early antitumor activity of the MEK-inhibitor binimetinib combined with cisplatin and pemetrexed.

METHODS

Eligible patients (pts) had stage III-IV NSCLC unsuitable for curative treatment, KRAS exon 2 or 3 (codon 12, 13 or 61) mutations, no prior systemic therapy. Pts were enrolled into part 1: 3 + 3 design with dose escalation in 2 dose levels (DL) of binimetinib and part 2: expansion cohort at the maximum tolerated dose (MTD). Pts received 4 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2and binimetinib 30 (DL1)/45 mg (DL2) orally twice a day (bid) d1-14 q3w followed by pemetrexed and binimetinib until progressive disease (PD) or unacceptable toxicity.

RESULTS

From May 2017 to Dec 2019, 18 pts (13 dose escalation, 5 expansion cohort) were enrolled. Median age was 60 (48-73, range). KRAS mutations were 87.5 % at codon 12. No DLT occurred in the dose escalation cohort. Median number of cycles was 2 (1-17, range). Treatment discontinuation was mainly due to PD (33 %) or pts/physicians' decision (27 %). Together with the expansion cohort, 16 pts were evaluable for safety. Most frequent treatment-related grade 3 AEs were lung infection (25 %), fatigue (19 %), anemia (19 %). Overall response rate among 9 evaluable pts receiving binimetinib at MTD (45 mg bid) was 33 % (7-70 %, 95 % CI). Median progression-free survival was 5.7 months (1.1-14.0, 95 % CI) and overall survival 6.5 months (1.8-NR, 95 % CI).

CONCLUSIONS

Pts treated with combination of cisplatin, pemetrexed and binimetinib presented no unexpected toxicity. No early signal of increased antitumor activity of binimetinib added to chemotherapy was observed in our pts population.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Oppliger Leibundgut, Elisabeth

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0169-5002

Publisher:

Elsevier

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

15 Jun 2021 13:38

Last Modified:

15 Jun 2021 13:38

Publisher DOI:

10.1016/j.lungcan.2021.04.002

PubMed ID:

33933896

Uncontrolled Keywords:

Binimetinib Chemotherapy KRAS mutation MEK inhibitors Non-small cell lung cancer Phase 1

BORIS DOI:

10.48350/156349

URI:

https://boris.unibe.ch/id/eprint/156349

Actions (login required)

Edit item Edit item
Provide Feedback