RAINFALL met its primary endpoint of improved progression-free survival (HR = 0.75, 95% CI 0.61–0.94, median 5.7 vs 5.4 months), but overall survival was not improved (HR = 0.96). No new safety signals were identified compared with other RAM studies. Here we present the QoL results.
Patients (pts) with untreated metastatic HER2- G-GEJ cancer were randomized to receive RAM (8 mg/kg D1, D8) or PL every 21 days. All pts received Cape (or 5FU) + Cis. Pts completed the EORTC QLQ-C30 (v3) at baseline (BL), before each cycle, and at 30-day follow-up. QoL scores were standardized to a 0-to-100 scale; ≥10-point change was considered clinically meaningful. Two pre-specified analyses were conducted using the ITT population: (1) time to sustained deterioration (TtSD) was from randomization to first worsened score with no subsequent improved or stable score and compared with an unstratified log-rank test; and (2) post-BL QoL assessments were classified as improved, stable, worsened, or not evaluable; rates of improved+stable were compared with Fisher’s exact test.Table: 616PD
Rates of improved and stable QoL scores for scales with greatest baseline impairment at select cycles
|RAM+Cape/Cis (N = 326), %||PL+Cape/Cis (N = 319), %|
|Cycle 2 Improved /Stable||Total||Cycle 4 Improved /Stable||Total||Cycle 2 Improved /Stable||Total||Cycle 4 Improved /Stable||Total|
|Global QoL||21.2 / 31.3||52.5||16.6 / 21.2||37.7||21.9 / 31.3||53.3||14.1 / 22.9||37.0|
|Emotional functioning||21.8 / 35.9||57.7||19.0 / 28.2||47.2||25.4 / 35.4||60.8||19.7 / 24.5||44.2|
|Fatigue||20.9 / 17.5||38.3||17.2 / 9.8||27.0||19.7 / 23.8||43.6||11.9 / 17.6||29.5|
|Pain||27.6 / 27.6||55.2||19.3 / 23.9||43.3||27.3 / 26.0||53.3||19.4 / 20.1||39.5|
|Insomnia||20.6 / 37.7||58.3||17.2 / 26.4||43.6||17.9 / 36.7||54.5||15.4 / 23.2||38.6|
|Appetite loss||21.2 / 33.4||54.6||16.6 / 24.8||41.4||20.7 / 33.2||53.9||16.0 / 21.3||37.3|
Of 645 pts randomized, 312/326 (96%) of RAM+Cape/Cis and 309/319 (97%) of PL+Cape/Cis pts had BL QoL data. Compliance was ≥87% with post-BL assessments while on therapy. BL scores were similar between arms. Based on BL mean scores, highest levels of impairment were seen for global QoL, emotional functioning, fatigue, pain, insomnia, and appetite loss. For all 15 QoL scales, TtSD HRs ranged from 0.80 to 1.13 and all 95% CIs included 1. For all scales and post-BL assessments, rates of improved+stable scores were similar between arms.
For pts with previously untreated, metastatic G-GEJ cancer, QoL was maintained with the addition of RAM to Cape/Cis. Regardless of arm, treatment improved or stabilized most disease-related symptoms.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company.
Eli Lilly and Company.
Eli Lilly and Company contracted with Syneos Health for writing support provided by Andrea Humphries, PhD and editorial support provided by Angela C. Lorio, ELS.
I. Chau: Advisory board: Sanofi Oncology, Eli-Lilly, Bristol-Myers Squibb, MSD, Bayer, Roche, Merck Serono, Five Prime Therapeutics; Research funding: Eli-Lilly, Janssen-Cilag, Sanofi Oncology, Merck-Serono, Novartis; Honorarium: Taiho, Pfizer, Amgen, Eli-Lilly. S-E. Al-Batran: Advisory role: Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol-Myers Squibb, MSD Sharp & Dohme; Speaker: Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, promedicis, Forum für Medizinische Fortbildung; CEO/founder of IKF Klinische Krebsforschung GmbH; Research grants: Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, German Cancer Aid (Krebshilfe), German Research Foundation and the Federal Ministry of Education and Research. G. Bodoky: Consulting or advisory role: Bayer, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche; Travel, Accommodations, Expenses: Janssen, Lilly, Novartis, Pfizer, Roche. G. Folprecht: Honoraria: Merck KGaA; Consulting or advisory role: Baxalta, Bristol-Myers Squibb, Lilly/ImClone, Merck KGaA, Roche/Genentech; Research funding: Merck KGaA. K. Peltola: Personal fees: Orion Pharma, BMS, Pfizer, Roche, MSD, Ipsen, outside the submitted work; Advisory fees and Stock holder: Faron Pharmaceuticals. C. Denlinger: Honoraria: Eli Lilly and Co; Research support (institutional): Eli Lilly and Co, MedImmune, AstraZeneca, Merrimack, Bristol-Myers Squibb, Genentech. A. Liepa, M. Das, R. Wei: Employee, Stockholder: Eli Lilly and Company. C.S. Fuchs: Consultant fees: Lilly, Entrinsic Health, Genentech, Merck, Sanofi, Five Prime Therapeutics, Merrimack, Bayer, Agios, Taiho, Kew, Bain Capital, Unum; Board member: CytomX. All other authors have declared no conflicts of interest.