Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

Figures & data

Figure 1 Schematic representation of proactive regimens A and B.

Notes: ^aTaken 30 minutes before ceritinib dose. All agents to be taken orally. Patients were tapered off proactive treatment based on symptoms.

Abbreviations: bid, twice daily; d, dose; PRN, as needed; Q4h, every 4 hours; Q6h, every 6 hours; qd, once daily.

Table 1 Patient characteristics

	Patient
	1	2	3	4	5	6	7	8	9
Age at enrollment, years	64	54	62	72	53	57	81	48	41
Line of therapy	Third	Second	Fourth	Fifth	Fifth	Third	Third	Fourth	Third
Previous regimens	• Carbo/PEM • Crizotinib	• P/Carbo + RT	• Carbo/PEM • P • Crizotinib	• P/Carbo • DTX • PEM + Bev • Crizotinib	• Erlotinib • P/Carbo • PEM • Crizotinib	• Carbo/PEM + Bev • Crizotinib	• Carbo/DTX • Crizotinib	• P/Carbo + Bev • Crizotinib • P/Cis	• Cis/PEM • Crizotinib
Other previous therapies	WBRT	Chest RT	WBRT	Chest RT	None	None	Craniotomy in Jul 2013; SRS in Jul 2013	None	SRS Apr 2012
Reasons for discontinuation of previous therapy	PD	PD	PD	PD	PD	Intolerance	Intolerance; brain and bone lesions	Brain metastasis	PD in brain (LC)
Time on ceritinib treatmenta	4 months: Nov 2013–Mar 2014	5 months: Oct 2012–Mar 2013	>16 months: Mar 2014–Aug 2015 (ongoing with dose reduction to600 mg/d due to Gr 3 transaminitis)	2 weeks: Nov 2013	20 months: Jan 2013–Aug 2014	2 months: Mar 2014–Apr 2014	>23 months: Aug 2013–Aug 2015 (ongoing at 750 mg/d)	4 months: Jul 2013–Oct 2013	2 months: Mar 2014–Apr 2014 (compassionate use – transferred to commercial drug)
Reasons for discontinuation of ceritinib	New primary malignancy	Comorbidity	Ongoing	Abdominal cramps, diarrhea	PD	PD	Ongoing	PD in brain	PD/death
Initial regimen	Regimen A				Regimen B
	Ondansetron and diphenoxylate/atropine	Ondansetron and loperamide	Ondansetron and diphenoxylate/atropine	Ondansetron and diphenoxylate/atropine	Ondansetron, dicyclomine, and loperamide
Other agents added	None	Lorazepam, dicyclomine, and dronabinol	None	None	Diphenoxylate/atropine for persistent diarrhea

Note:

a Treated at University of Washington for patients 1–4 and Highlands Oncology Group for patients 5–9.

Abbreviations: Bev, bevacizumab; Carbo, carboplatin; Cis, cisplatin; DTX, docetaxel; Gr, grade; LC, leptomeningeal carcinomatosis; P, paclitaxel; PD, progressive disease; PEM, pemetrexed; RT, radiotherapy; SRS, stereotactic radiosurgery; WBRT, whole-brain radiotherapy.