Author of

• 20167

  +

  P2.03 - Chemotherapy/Targeted Therapy (ID 704)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Chemotherapy/Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23329

    +

    P2.03-058 - Tiger-3: A Phase 3 Randomized Study of Rociletinib Vs Chemotherapy in EGFR-mutated Non-small Cell Lung Cancer (NSCLC) (ID 8395)

    09:30 - 09:30  |  Author(s): L. Rolfe
    • Abstract

    Background:
    Rociletinib, an oral, irreversible tyrosine kinase inhibitor (TKI), selectively targets activating mutations in EGFR and the acquired resistance mutation T790M and demonstrated antitumor activity in the phase 1/2 TIGER-X study (NCT01526928). Initial results are reported from the TIGER-3 study (NCT02322281) of rociletinib vs chemotherapy in EGFR TKI-resistant patients with EGFR-mutated NSCLC.
    
    Method:
    Eligibility criteria included: metastatic or unresectable, locally advanced, EGFR-mutated NSCLC; radiological progression on most recent TKI therapy; ≥1 line of platinum doublet chemotherapy. Patients were not selected based on T790M status. Patients (N=900) were to be randomized (1:1:1) to rociletinib 500 or 625 mg BID or investigator’s choice of chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). The primary endpoint was investigator-assessed progression-free survival (PFS) (RECIST v1.1); objective response rate (ORR) was a secondary endpoint. The rociletinib dosing groups were combined and compared with chemotherapy in a step-down procedure (patients with a centrally confirmed T790M mutation, followed by all randomized patients).
    
    Result:
    TIGER-3 enrollment was halted upon discontinuation of rociletinib development in NSCLC in 2016; therefore, target enrollment was not achieved. TIGER-3 enrolled 75 patients in the rociletinib groups [500 mg BID, n=53; 625 mg BID, n=22] and 74 in the chemotherapy group. Median age was 62 years, 69.1% had ECOG Performance Status of 1, 39.6% were Asian, 58.4% were female, and median number of prior therapies was 3. PFS and ORR data are presented in the Table. The most common adverse events (all grade; grade ≥3) in the rociletinib group were diarrhea (62.7%; 2.7%), hyperglycemia (58.7%; 24.0%), nausea (37.3%; 4.0%), fatigue (37.3%; 8.0%), and decreased appetite (37.3%; 0%) and in the chemotherapy group were nausea (27.4%; 5.5%), anemia (24.7%; 2.7%), and fatigue (24.7%; 9.6%).

    Outcome	Centrally Confirmed T790MPositive		Centrally Confirmed T790MNegative		Intent-to-Treat Population*
    	Rociletinib[†] (n=25)	Chemotherapy (n=20)	Rociletinib[†] (n=36)	Chemotherapy (n=41)	Rociletinib[†] (n=75)	Chemotherapy (n=73)
    Median PFS, mo (95% CI)	6.8 (3.7–12.2)	2.7 (1.3–7.0)	4.1 (2.5–4.6)	1.4 (1.3–2.7)	4.1 (2.8–5.5)	2.5 (1.4–2.9)
    HR (95% CI)	0.570 (0.285–1.140); P=0.105		0.532 (0.322–0.878); P=0.011		0.609 (0.423–0.875); P=0.006
    Confirmed ORR, n (%) [95% CI]	9 (36.0) [18.0%–57.5%]	3 (15.0) [3.2%–37.9%]	3 (8.3) [1.8%–22.5%]	2 (4.9) [0.6%–16.5%]	13 (17.3) [9.6%–27.8%]	6 (8.2) [3.1%–17.0%]
    *Includes patients with undetermined T790M mutation status. [†]Rociletinib 500 mg BID and 625 mg BID dose groups were pooled for the analysis. CI, confidence interval; HR, hazard ratio.

    
    
    Conclusion:
    Incomplete enrollment precluded hypothesis testing. However, the data show a trend toward longer PFS and higher ORR with rociletinib.