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Carmen Kahatt
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P1.12 - Small Cell Lung Cancer/NET (ID 179)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.12-03 - Antitumor Activity of Single Agent Lurbinectedin in Patients with Relapsed SCLC Occurring ≥30 Days After Last Platinum Dose (ID 1710)
09:45 - 18:00 | Author(s): Carmen Kahatt
- Abstract
Background
Lurbinectedin (L) inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis.
Method
This multicenter, single agent, phase II Basket trial treated a cohort of 105 SCLC patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line. L 3.2 mg/m2 was administered as a 1-hour i.v. infusion on Day 1 q3wk. Primary endpoint, confirmed overall response rate (ORR) by RECIST v.1.1 according to investigator assessment, was met (ORR=35.2%; 95% CI, 26.2-45.2%). A sub-analysis excluding the 21 pts with disease relapse < 30 days after last platinum dose is reported here.
Result
Median age of 84 evaluated pts was 60 years (range, 41-83), 58.3% were male, ECOG PS 0-1/2 in 96/4%, liver metastasis in 36.9%, history of CNS involvement in 4.8%, prior platinum in 100%, median chemotherapy-free interval (CTFI)=3.9 months (1.1-16.1); prior immunotherapy in 8.3%. A median of 5.5 cycles (range, 1-24) was administered.
ORR, % (95% CI) (confirmed responses) (n=84)
40.5 (29.9-51.7)*
CTFI≥90d (n=60)
45.0 (32.1-58.4)
CTFI 30-89d (n=24)
29.2 (12.6-51.1)
Disease Control Rate at 6 months, % (n=84)
48.8
Median duration of response (months) (95% CI) (n=34)
5.3 (3.5-6.4)
CTFI≥90d (n=27)
6.2 (3.5-7.3)
CTFI 30-89d (n=7)
4.1 (2.6-5.3)
Median overall survival (months) (95% CI) (n=84)**
10.9 (7.8-14.9)
CTFI≥90d (n=60)**
11.9 (9.7-16.2)
CTFI 30-89d (n=24)**
(4.1-7.6)
*4 of 7 pts who failed prior immunotherapy had confirmed response
**Preliminary data
L was well tolerated. Neutropenia was the most common adverse event (AE) (G3:21.5% and G4:25%), whereas febrile neutropenia was reported in 2.4%. Most common non-hematological AEs included fatigue (G3: 7.1%), nausea and vomiting (all G1-2: 32.1% and 16.7%) and transaminase increase (G3:7.2%). There was no death due to treatment related AE.
Conclusion
L is an active agent for second-line treatment of SCLC. The highest ORR (45.0%) was reported for pts with CTFI≥90d. Notable antitumor activity (ORR=29.2%) was also observed in pts with CTFI 30-89d, for whom no therapy is currently approved. Hence, L is a valuable therapeutic option for SCLC pts with disease relapse after first-line platinum-based therapy.
Updated trial results will be presented at the conference.
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P2.12 - Small Cell Lung Cancer/NET (ID 180)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.12-13 - Lurbinectedin (L) Combined with Paclitaxel (P) or Irinotecan (I) in Relapsed SCLC. Results from Two Phase Lb Trials (ID 1588)
10:15 - 18:15 | Author(s): Carmen Kahatt
- Abstract
Background
L is a new agent that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment. Preclinical evidence of synergism was observed for L in combination with P and I.
Method
Activity of combinations with LP and LI in small cell lung cancer (SCLC) was reviewed in two phase Ib trials. Patients were enrolled following a 3+3 dose escalation design. SCLC patients with ECOG performance status (PS) 0-1 and pretreated with at least one platinum-based chemotherapy are presented. Extensive pharmacokinetic (PK) sampling for L and P or I was performed.
Result
19 pts were treated: 7 with LP and 12 with LI. Baseline characteristics (LP/LI) were: males, 57%/45%; median age, 55/57 years; ECOG PS score 1, 57%/92%; chemotherapy-free interval (CTFI) >90 days, 43%/67%; median (range) prior lines, 1 (1-3)/2 (1-3); liver metastases, 29%/33%.
Lurbinectedin-Paclitaxel
(L: 2.2 mg/m2 – 5 mg FD +
P: 60-80 mg/m2) *
(n=7)
Lurbinectedin-Irinotecan
(L: 1-2.4 mg/m2 + I: 75 mg/m2) **
(n=12)
ORR (CR+PR)
CR
PR
71% (n=5)
14% (n=1)
57% (n=4)
25% (n=3)
0%
25% (n=3)
ORR in CTFI >90d
67%
38%
CB (CR+PR+SD≥4m)
71%
67%
Median DOR
2.3 m 95% CI (2.0-NR)
4.6 m 95% CI (3.0-6.8)
Median PFS
4.8 m 95% CI (1.8-12.5)
5.6 m 95% CI (1.4-8.3)
* Combination with P given for up to 6 cycles, followed by single-agent L 2.2 mg/m2.
** One patient received L 3 mg/m2 + I 15 mg/m2.
CB, clinical benefit; CR, complete response; CTFI, chemotherapy-free interval; d, days; DOR, duration of response; FD, flat dose; I, irinotecan; L, lurbinectedin; m, months; NR, not reached; ORR, overall response rate; P, paclitaxel; PFS, progression-free survival; PR, partial response; SD, stable disease.
Adverse events (AEs): grade (G) 4 neutropenia LP/LI 43%/27% of patients; no episodes of febrile neutropenia in LI, one (G3) in LP; no G4 anemia or G4 thrombocytopenia in either study. Non-hematological toxicity was mild and mainly consisted of G3 fatigue (18%) and G3 nausea (7%) in LI; no G3/4 toxicities were found in LP. No toxic deaths and no discontinuations were due to AEs. PK: mean clearance of L (12 L/h in combo with P, and 9.5 L/h in combo with I), of P (31.5 L/h) and of I (32.2 L/h) are comparable with reported data (11.2 L/h, 31.4/h and 25 L/h, respectively).
Conclusion
LP and LI combinations showed promising activity after first-line therapy in SCLC. This activity seems consistent with that observed in other trials with L given alone or in combination. Both combinations showed acceptable safety profile. So far, no evidence of major PK drug-drug interactions has been observed. Further development of these combinations is warranted.