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Observational Study
. 2017 Feb;15(1):31-41.e4.
doi: 10.1016/j.clgc.2016.10.008. Epub 2016 Oct 29.

Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM

Joseph I Clark  1 , Michael K K Wong  2 , Howard L Kaufman  3 , Gregory A Daniels  4 , Michael A Morse  5 , David F McDermott  6 , Sanjiv S Agarwala  7 , Lionel D Lewis  8 , John H Stewart  5 , Ulka Vaishampayan  9 , Brendan Curti  10 , René Gonzalez  11 , Jose Lutzky  12 , Venkatesh Rudraptna  13 , Lee D Cranmer  14 , Joanne M Jeter  15 , Ralph J Hauke  16 , Gerald Miletello  17 , Mohammed M Milhem  18 , Asim Amin  19 , John M Richart  20 , Mayer Fishman  21 , Sigrun Hallmeyer  22 , Sapna P Patel  23 , Peter Van Veldhuizen  24 , Neeraj Agarwal  25 , Bret Taback  26 , Jonathan S Treisman  27 , Marc S Ernstoff  28 , Jessica C Perritt  29 , Hong Hua  29 , Tharak B Rao  29 , Janice P Dutcher  30 , Sandra Aung  29
Affiliations
Observational Study

Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM

Joseph I Clark et al. Clin Genitourin Cancer. 2017 Feb.

Abstract

Background: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2).

Patients and methods: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in ProleukinR Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015.

Results: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2.

Conclusions: HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients.

Keywords: Anti-VEGF therapy; Cytokine; Kidney cancer; Therapy trends; Toxicity.

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Conflict of interest statement

Disclosure

Dr Amin Asim reports Speakers’ Bureau support from BMS, Merck, and Pfizer; Dr Brendan D. Curti reports travel, accommodations, and expenses support from Agonox, BMS, and Prometheus; research funding from Prometheus and Galectin Therapeutics; honoraria from Prometheus Laboratories Inc; Speakers’ Bureau support from Prometheus; and is also an unpaid consultant for Agonox and Ubivac; Dr Bret Taback reports Speakers’ Bureau support from Prometheus; Dr David F. McDermott has performed in a consulting or advisory role for Merck, Genentech, Novartis, Pfizer, and BMS; Dr Hong Hua is an employee of Prometheus Laboratories Inc; Dr. Howard L. Kaufman reports honoraria from Alkermes, Amgen, EMD Serono, Merck, Prometheus, and Sanofi; Speakers’ Bureau support from Merck; and has performed in a consulting or advisory role for Prometheus, Alkermes, Amgen, EMD Serono, Merck, and Sanofi; Dr Janice P. Dutcher has performed in a consulting or advisory role for Prometheus, BMS, Tracon, Amgen (Data Safety and Monitoring Committees), Novartis (education); and has received Speakers’ Bureau support from Prometheus and Novartis; Dr Jonathan S. Treisman has performed in an advisory role for Prometheus Laboratories Inc; has received Speakers’ Bureau support from Prometheus Laboratories Inc; and has received travel, accommodations, and expenses from Prometheus (speaking, advisory); Dr Joseph I. Clark is an advisory board member for Prometheus and Bayer-Onyx; has received Speakers’ Bureau support from Prometheus, BMS, and Merck; and has received honoraria from Prometheus, BMS, Pfizer, and Merck; Dr Mayer Fishman participated in RCC-related advisory boards for Aveo, Bayer, Eisai, GSK (now part of Novartis), Novartis, Pfizer, and Prometheus; and has received research funding for RCC-related trials from Acceleron, Altor, Aveo, Bayer, Eisai, Exelixis, GSK (now part of Novartis), Merck, Pfizer, Prometheus, and Tracon; Dr Michael A. Morse is an advisory board member for Genentech, Prometheus, Celgene, Ipsen, Novartis, and Lexxicon; has received Speakers’ Bureau support from Genentech, Prometheus, Celgene, and Novartis; has received honoraria from Genentech, Prometheus, Celgene, Ipsen, Novartis, Astellas Bayer, Onyx, and Lexxicon; and has received research funding from BMS, Aduro, Alphavax, and Eisai; Dr Neeraj Agarwal has performed in a consulting or advisory role for Pfizer, Argos, and Exelixis; Dr Peter Van Veldhuizen has acted in a consulting or advisory role for Prometheus and has received Speakers’ Bureau support from Prometheus; Dr Ralph J. Hauke has received honoraria from Best Doctors for second opinion consultations; Dr Rene Gonzalez is an advisory board member for Bayer-Onyx, BMS, Genentech, GSK, Prometheus, and Roche; and has received research funding from Bayer, BMS, Eisai, Genentech, GSK, Merck, Novartis, Pfizer, Prometheus, and Roche; Dr Sandra Aung is an employee of Prometheus Laboratories Inc; Dr Sigrun Hallmeyer has received travel, accommodations, and expenses from BMS as part of Speakers’ Bureau; has served in a consulting or advisory role for BMS, Cardinal Health, iCAN, and TPI; has received Speakers’ Bureau support from BMS; and is a member of the Board of Directors for Oncology Specialists SC; Dr Tharak Rao is an employee of Prometheus Laboratories Inc; Dr Ulka Vaishampayan received honoraria and research funding from Prometheus Laboratories Inc; Jessica Perritt is an employee of Prometheus Laboratories Inc. Dr Venkatesh Rudrapatna has stated that he has no conflicts of interest.

Figures

Figure 1
Figure 1
Overall Survival. A, Analysis Population, n [ 352. Data Was Available for All 352 Patients; of These, 116 Were Confirmed Deceased and 236 Were Known to Be Alive at the Last Follow-up Date of September 24, 2015. The Overall Survival Data (Not Reached [NR]) Was Calculated From the Time of Starting High-dose Interleukin-2 (HD IL-2) Therapy. The Median Follow-up Was 21 Months. Vertical Bars Represent Censored Subjects. B, Overall Survival by Response to HD IL-2. Response Rate Was Available for 328 of 352 Patients. The Median Overall Survival (mOS) for Patients With Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Was Not Reached. One Hundred Forty-Two Patients With Progressive Disease (PD) After HD IL-2 Experienced an mOS of 15.5 Months. Vertical Bars Represent Censored Subjects
Figure 2
Figure 2
Kaplan-Meier Overall Survival by the International mRCC Database Consortium Risk Factors. Six Risk Factors Were Considered Using the International mRCC Database Consortium Prognostic Model. Patients Were Grouped Into 3 Categories: Favorable [ 0, Intermediate [ 1–2, Poor [ 3 D Risk Factors. Two Hundred Seventy-One Patients had Complete Data for All 6 Prognostic Factors and Were Included in the Analysis. Fifty Patients Were in the Favorable Group, 196 Were in the Intermediate Group, and 25 Were in the Poor Group. Vertical Bars Represent Censored Subjects Abbreviations: mOS = median overall survival; mRCC = metastatic renal cell carcinoma; NR = not reached.
Figure 3
Figure 3
Kaplan-Meier Overall Survival of Patients Receiving Prior Targeted Therapy (TT). A, Overall Survival of All Patients in the Prior TT Group. B, Overall Survival of Patients in the Prior TT Group by Response to High-dose Interleukin-2 (HD IL-2). Vertical Bars Represent Censored Subjects Abbreviations: CR = complete response; mOS = median overall survival; NR = not reached; PD = progressive disease; PR = partial response; SD = stable disease.
Figure 4
Figure 4
Kaplan-Meier Overall Survival in Patients With HD IL-2 Alone or Post-targeted Therapy (TT). A, Overall Survival of Patients in the Post TT Only Group Compared With No TT Group (P = .88). B, Overall Survival of Patients in the Post TT Only Group by Response to High-dose Interleukin-2 (HD IL-2). Vertical Bars Represent Censored Subjects. C, Overall Survival of Patients in the No TT Group by Response to HD IL-2. Vertical Bars Represent Censored Subjects Abbreviations: CR = complete response; mOS = median overall survival; NR = not reached; PD = progressive disease; PR = partial response; SD = stable disease.
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