177Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial

Article Figures & Data

TABLE 1.

Patient Characteristics

Variable	n
Sex
Male	11
Female	7
Performance status
0	8
1	10
Age (y)	65.5 (42–84)
Ki-67	15
<3%	0
3%–20%	10
>20%	5
Tumor type
Pancreatic NETs	7
Small intestinal NETs	4
AC lung NETs	4
Other^*	3
Metastatic disease	17
Previous lines of systemic therapy
0–1	8
2–3	9
>3	1
Previous therapies
Somatostatin analogs	14
Chemotherapy	11^†
Surgery	8
mTOR inhibitor or tyrosine kinase inhibitor	7
Other^‡	6

↵* Meningioma, medullary thyroid cancer, and unknown NET.
↵† One patient received systemic chemotherapy because of different malignancy after NET diagnosis.
↵‡ External radiation, liver embolization, or liver radioembolization.
AC = atypical carcinoid.
Age is median followed by range in parentheses.

TABLE 2.

Cycles, Escalated Dose of Olaparib, and DLT

Patient	Cycles (n)	Reached dose of olaparib	DLT	Other reason for hampered escalation
Cohort 1
1	2	100 mg BID		Progressive disease after 2 cycles^*
2	4	300 mg BID
4	4	200 mg BID		Abdominal pain G1^†
5	2	100 mg BID		Progressive disease after 2 cycles^*
6	4	300 mg BID
7	2	50 mg BID		Noncompliant^*
8	4	100 mg BID		Fatigue G2, nausea G2, loss of appetite G2
9	4	300 mg BID
10	4	300 mg BID
11	4	300 mg BID^‡	Thrombocytopenia G3
12	4	300 mg BID
Cohort 2
13	4	300 mg BID^‡	Thrombocytopenia G3
14	3	100 mg BID		Thrombocytopenia G2
15	4	300 mg BID
16	4	300 mg BID^‡		Thrombocytopenia G2
17	1	0 mg		Carcinoid reaction on first ¹⁷⁷Lu infusion^*
19	2	200 mg BID		Progressive disease after 2 cycles^*
20	4	300 mg BID^‡	Thrombocytopenia G3

↵* Premature study discontinuation.
↵† Not escalated at cycle 1 because of abdominal pain G1, so did not reach 300 mg.
↵‡ Discontinued last cycle of olaparib.
G1 = grade 1; G2 = grade 2; G3 = grade 3.
Patients 3 and 18 were excluded from the study.

TABLE 3.

Adverse Events in at Least 3 Patients

Adverse event	Grade 1	Grade 2	Grade 3	Grade 4
Anemia	11 (61)	5 (28)
Thrombocytopenia	6 (33)	3 (17)	5 (28)
Leucopenia	4 (22)	6 (33)	3 (17)
Lymphocytopenia	1 (6)	5 (28)	10 (56)	1 (6)
Neutropenia	1 (6)	5 (28)	3 (17)
Nausea	11 (61)	3 (17)
Fatigue	9 (50)	4 (22)	1 (6)
AST increased	8 (44)
Hyponatremia	5 (28)	1 (6)
Hypochloremia	5 (28)
Diarrhea	5 (28)
Hypokalemia	5 (28)
ALT increased	4 (22)	2 (11)
ALP increased	4 (22)	1 (6)
Weight loss	4 (22)	1 (6)
Bicarbonate increased	4 (22)
Alopecia	4 (22)
Abdominal pain	3 (17)	1 (6)	1 (6)
Creatinine increased	3 (17)	1 (6)
Dizziness	3 (17)	1 (6)
Dyspnea	3 (17)
Bilirubin increased	2 (11)	1 (6)	1 (6)
Hypotension	2 (11)	2 (11)
Constipation	2 (11)	1 (6)
Pain	1 (6)	2 (11)	1 (6)

AST = aspartate transaminase; ALT = alanine transaminase; ALP = alkaline phosphatase.
Data are number followed by percentage in parentheses.

TABLE 4.

Ongoing Studies with ¹⁷⁷Lu-PRRT and PARP Inhibitors

Study	Phase	n	Reference
¹⁷⁷Lu-DOTATATE in combination with olaparib in metastatic or inoperable gastrointestinal NETs	I–II	33	(16)
¹⁷⁷Lu-DOTATATE in combination with olaparib in recurrent or relapsed solid tumor expressing somatostatin receptor (children and adolescents)	II	25	NCT06607692
¹⁷⁷Lu-DOTATATE in combination with olaparib in locally advanced or metastatic NETs	I	24	NCT05870423
¹⁷⁷Lu-DOTATATE in combination with talazoparib in NETs	I	24	NCT05053854
¹⁷⁷Lu-DOTATATE in combination with olaparib in inoperable GEPNETs	I–II	42	NCT04086485