The solitary fibrous tumour (SFT) is a rare tumour, which usually occurs in the pleura. Patients with an advanced SFT have a poor prognosis. The treatment options for recurrent disease are especially limited. We present the case of a 55-year-old female patient with a malignant SFT of the pleura, who received conventional chemotherapy and targeted therapy. This paper focuses on systemic therapy in the treatment of metastatic SFT.
9004 Background: In the ongoing phase 3 ARCHER 1050 study, first-line treatment with daco significantly improved the primary endpoint of progression-free survival, duration of response, and time to treatment failure vs gef in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) (Wu et al, Lancet Oncol, 2017). Here, we present the OS results. Methods: Pts with newly diagnosed stage IIIB/IV or recurrent NSCLC harboring an EGFR mutation (exon 19 del or exon 21 L858R ± exon 20 T790M) and without central nervous system metastasis were randomized 1:1 to oral daco 45 mg/day or oral gef 250 mg/day. Pts were stratified by race and EGFR mutation type. Results: As of 17 February 2017, a total of 220 deaths (48.7%) occurred over a median follow-up of 31.3 months (mo): 103 (45.4%) in the daco arm (n = 227) and 117 (52.0%) in the gef arm (n = 225). Daco showed a significant improvement in OS compared to gef (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.582–0.993; 2-sided P = 0.044 based on stratified analysis). Median OS (95% CI) was 34.1 mo (29.5–37.7) with daco vs 26.8 mo (23.7–32.1) with gef. Survival rates at 30 mo were 56.2% with daco and 46.3% with gef. The table shows preliminary OS subgroup analyses by race and EGFR mutation type, with >55% of pts being censored in some subsets. OS subgroup analyses were consistent with the primary OS analysis across most baseline characteristics. Conclusions: In pts with advanced EGFR mutation-positive NSCLC, daco is the first to show a significant improvement in OS in a phase 3 trial compared with a standard-of-care tyrosine kinase inhibitor. Daco should be considered as one of the standard treatment options for these pts. Clinical trial information: NCT01774721. Daco (n = 227) Gef (n = 225) Daco vs Gef, HR (95% CI) 2-Sided P Value n Median OS, mo (95% CI) n Median OS, mo (95% CI) Race Non-East Asian 57 29.5 (20.7–NR) 49 20.6 (16.1–25.5) 0.721 (0.433–1.201) 0.2073 Asian 170 34.2 (30.1–NR) 176 29.1 (25.2–NR) 0.812 (0.595–1.108) 0.1879 EGFR mutation status at randomization Exon 19 del 134 34.1 (30.1–NR) 133 NR (25.0–NR) 0.880 (0.613–1.262) 0.4862 Exon 21 L858R 93 32.5 (25.5–NR) 92 23.2 (19.6–28.6) 0.707 (0.478–1.045) 0.0805 NR, not reached
Abstract Introduction: Checkpoint inhibitors have demonstrated activity in brain lesions in several tumor types, including NSCLC. CheckMate 227 Part 1 (NCT02477826) met its two independent co-primary endpoints, including improved overall survival (OS) for NIVO + IPI vs histology-based chemotherapy (chemo) in patients (pts) with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. Benefit was also observed in pts with PD-L1 < 1%. Eligible pts included those with treated, asymptomatic brain metastases (mets). Here we present a post-hoc analysis of efficacy and safety in pts with and without baseline (BL) brain mets. Methods: Eligible pts were chemo-naive, with stage IV or recurrent NSCLC, no known sensitizing EGFR/ALK alterations, and ECOG PS 0–1. Pts with treated brain mets who were asymptomatic for ≥ 2 wks prior to randomization were eligible; corticosteroids equivalent to ≤ 10 mg of prednisone daily were permitted if stable or decreasing for ≥ 2 wks prior to randomization. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or chemo; pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 360 mg Q3W + chemo, or chemo. Pts were treated until disease progression, unacceptable toxicity, or ≤ 2 y of immunotherapy. Results: BL characteristics were generally similar between pts with and without BL brain mets, except that a greater proportion of pts with BL brain mets were < 65 years of age and had non-squamous histology. Efficacy data are shown in the Table. Any-grade nervous system adverse events were reported in 46% of pts with BL brain mets treated with NIVO + IPI and 42% of those treated with chemo, most were grade 1–2. Conclusion: In this post-hoc analysis of pts with advanced NSCLC, NIVO + IPI appeared to provide similar benefit in pts with and without BL brain mets. No new safety signals were identified. Table.Efficacy by baseline brain metastases in CheckMate 227 Part 1Patients with baseline brain metastasesPatients without baseline brain metastasesNIVO + IPI (n = 69)Chemo (n = 66)NIVO + IPI (n = 514)Chemo (n = 517)OS, median (95% CI), mo18.8 (9.2-29.4)13.7 (10.5-16.2)17.1 (15.3-19.9)13.9 (11.8-15.3)HR (95% CI)0.57 (0.38-0.85)0.76 (0.66-0.88)1-y rates, %575962542-y rates, %44264030PFS,a median (95% CI), mo5.4 (3.1-8.6)5.8 (4.3-8.0)4.9 (4.1-5.7)5.4 (4.5-5.6)HR (95% CI)0.79 (0.52-1.19)0.81 (0.70-0.93)1-y rates, %382132172-y rates, %227206ORR,a %33263328DOR,a median (95% CI), mo24.9 (11.3-NR)8.4 (4.2-13.9)19.6 (15.5-28.6)5.8 (4.8-6.9)1-y rates, %724065262-y rates, %5384610Minimum follow-up was 29.3 mo.aPer BICR. BICR, blinded independent central review; CI, confidence interval; chemo, chemotherapy; DOR, duration of response; HR, hazard ratio; IPI, ipilimumab; mo, month; NIVO, nivolumab; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; y, year. Citation Format: Hossein Borghaei, Adam Pluzanski, Reyes Bernabe Caro, Mariano Provencio, Sjaak Burgers, Enric Carcereny, Keunchil Park, Aurelia Alexandru, Lorena Lupinacci, Randeep Sangha, Judith Raimbourg, Alain Vergnenegre, Konstantinos Syrigos, Fabrice Barlesi, Norbert Frickhofen, Ang Li, Ravi Kasinathan, Luis Paz-Ares. Nivolumab (NIVO) + ipilimumab (IPI) as first-line (1L) treatment for patients with advanced non-small cell lung cancer (NSCLC) with brain metastases: Results from CheckMate 227 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT221.
8009 Background: Treatment options are limited for patients (pts) with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC). We report results of a randomized, open-label, global phase III study of NIVO, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, vs DOC in pts with SQ NSCLC and with disease progression (PD) during/after one prior PT-DC regimen. Methods: Pts (N = 272) were randomized 1:1 to receive NIVO 3 mg/kg (n = 135) Q2W or DOC 75 mg/m2(n = 137) Q3W until PD, discontinuation due to toxicity, or other reasons. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), quality of life, and safety. Results: Superior OS was observed with NIVO vs DOC (HR = 0.59; 95% CI: 0.44, 0.79; p = 0.00025). NIVO improved PFS vs DOC (HR = 0.62; 95% CI: 0.47, 0.81; p = 0.0004). ORR was 20% (27/135) for NIVO and 9% (12/137) for DOC (p = 0.0083). OS HRs favored NIVO regardless of PD-L1 expression (Table). Grade 3–4 drug-related AEs occurred in 7% (9/131) of NIVO and 55% (71/129) of DOC pts. No deaths were related to NIVO vs 3 DOC-related deaths. Conclusions: CheckMate 017 met its primary objective, demonstrating superior OS of NIVO vs DOC in pts with advanced, previously treated SQ NSCLC and demonstrated PFS and ORR superiority. Tumor PD-L1 status was neither prognostic nor predictive for efficacy endpoints. The safety profile of NIVO 3 mg/kg Q2W is acceptable and favorable vs DOC. NIVO represents a significant improvement in second-line therapy for SQ NSCLC. Clinical trial information: NCT01642004. NIVO (n = 135) DOC (n = 137) mOS, mo (95% CI) 9.2 (7.3, 13.3) 6.0 (5.1, 7.3) 1-yr OS, % (95% CI) 42 (34, 50) 24 (17, 31) Median duration of response, mo (range) Not Reached (2.9–20.5+) 8.4 (1.4+–15.2+) mPFS, mo (95% CI) 3.5 (2.1, 4.9) 2.8 (2.1, 3.5) 1-yr PFS, % (95% CI) 21 (14, 28) 6 (3, 12) PD-1 expression NIVO (n) DOC (n) OS HR (95% CI) ≥ 1% 63 56 0.69 (0.45, 1.05) < 1% 54 52 0.58 (0.37, 0.92) ≥ 5% 42 39 0.53 (0.31, 0.89) < 5% 75 69 0.70 (0.47, 1.02) ≥ 10% 36 33 0.50 (0.28, 0.89) < 10% 81 75 0.70 (0.48, 1.01)
In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic and intracranial efficacy outcomes and safety by baseline brain metastasis status at 5 years' minimum follow-up.Treatment-naive adults with stage IV or recurrent NSCLC without EGFR or ALK alterations, including asymptomatic patients with treated brain metastases, were enrolled. Patients with tumor PD-L1 greater than or equal to 1% were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy; patients with tumor PD-L1 less than 1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy groups. Assessments included OS, systemic and intracranial progression-free survival per blinded independent central review, new brain lesion development, and safety. Brain imaging was performed at baseline (all randomized patients) and approximately every 12 weeks thereafter (patients with baseline brain metastases only).Overall, 202 of 1739 randomized patients had baseline brain metastases (nivolumab plus ipilimumab: 68; chemotherapy: 66). At 61.3 months' minimum follow-up, nivolumab plus ipilimumab prolonged OS versus chemotherapy in patients with baseline brain metastases (hazard ratio = 0.63; 95% confidence interval: 0.43-0.92) and in those without (hazard ratio = 0.76; 95% confidence interval: 0.66-0.87). In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ipilimumab (12% and 16%, respectively) than chemotherapy (0% and 6%). Fewer patients with baseline brain metastases developed new brain lesions with nivolumab plus ipilimumab (4%) versus chemotherapy (20%). No new safety signals were observed.With all patients off immunotherapy for more than or equal to 3 years, nivolumab plus ipilimumab continued to provide a long-term, durable survival benefit in patients with or without brain metastases. Intracranial efficacy outcomes favored nivolumab plus ipilimumab versus chemotherapy. These results further support nivolumab plus ipilimumab as an efficacious first-line treatment for patients with metastatic NSCLC, regardless of baseline brain metastasis status.
First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.
