Introduction

Medullary thyroid cancer (MTC) occurs either sporadically in 75% of cases or in an inherited autosomal dominant manner in type 2 multiple endocrine neoplasia [1]. Although MTC represents only 1.6% to 5% of all thyroid cancer diagnoses, it accounts for approximately 15% of thyroid cancer deaths [2-4]. Germline rearranged during transfection (RET) mutations are present in essentially all patients with hereditary MTC [5]. Somatic RET mutations occur in about 60% of patients with sporadic MTC [5].

Standard of care for unresectable recurrent or metastatic MTC includes multikinase inhibitors (MKIs) active against a number of kinases, such as RET, VEGFR2, EGFR, and MET [6, 7]. Although MKIs have demonstrated efficacy in MTC, off-target toxicities attributed primarily to non-RET kinase inhibition have affected patient experience and lead to frequent dose reduction and discontinuation [6]. Selpercatinib, a first-in-class highly selective and potent RET inhibitor, has demonstrated clinically meaningful and durable antitumor activity with a favorable safety profile in patients with advanced or metastatic RET-mutant MTC in the ongoing phase I/II LIBRETTO-001 trial (NCT03157128) [8]. Among 55 patients who were previously treated with the MKIs vandetanib, cabozantinib, or both, the primary endpoint of objective response rate (ORR), assessed by independent review committee, was 69% (95% confidence interval [CI], 55%–81%). Median duration of response (DoR) and progression-free survival (PFS) were not reached at a median follow-up of 14.1 and 16.7 months, respectively. The 1-year PFS rate was 92% and 82% among those who had never received vandetanib or cabozantinib and among those previously treated with these agents, respectively. Among 88 patients who were naïve to vandetanib and cabozantinib, the ORR was 73% (95% CI, 62%–82%). Median DoR and PFS were 22.0 and 23.6 months (95% CI, both could not be evaluated) at a median follow-up of 7.8 and 11.1 months, respectively. Based on these findings, selpercatinib is approved in multiple countries for the treatment of RET-altered thyroid cancers [9, 10].

There is limited published research on the impact of MTC on health-related quality of life (HRQoL) in patients. Diarrhea is a common paraneoplastic syndrome caused by high levels of calcitonin secreted by MTC, which can be debilitating and may lead to workplace absence and lost productivity [4]. In some instances, the diarrhea is so debilitating that the patient is essentially homebound. In fact, diarrhea is the sole presenting symptom in many patients with MTC, often leading to a prolonged workup for the etiology of the diarrhea involving multiple providers and tests, delay in MTC diagnosis, self-treatment, and even loss of confidence in health care. Additionally, diarrhea is a treatment-related adverse effect of vandetanib and cabozantinib, and many patients with MTC on treatment will experience an increase in diarrhea [11-13]. Therefore, prior exposure to vandetanib or cabozantinib may have an impact on patient outcomes with subsequent treatment.

An exploratory objective of the LIBRETTO-001 trial was to describe patient-reported disease-related symptoms and HRQoL during selpercatinib treatment, including time to improvement or worsening in patients with RET-mutant MTC by prior exposure or no prior exposure to vandetanib or cabozantinib. In this interim analysis, patient-reported disease-related symptoms and HRQoL findings are summarized descriptively.

Materials and Methods

The LIBRETTO-001 trial is an ongoing, global, multicenter, open-label, phase I/II study that enrolled patients with advanced or metastatic solid tumors, including RET-mutant MTC, beginning in May 2017 [8]. Once determined, the recommended phase II dose of selpercatinib, 160 mg orally twice daily, was administered in 28-day cycles until disease progression, death, unacceptable toxicity, or withdrawal of consent. Selpercatinib treatment could continue, at the discretion of the investigator, in patients deriving clinical benefit despite disease progression. Eligible patients were 18 years of age or older (or as young as 12 years of age in countries/sites where approved) with an Eastern Cooperative Oncology Group performance status score of 0 to 2. Patients may have received prior MKIs or other systemic therapies at study enrollment. The primary endpoint was ORR assessed by an independent review committee using RECIST version 1.1. Secondary endpoints included duration of response, progression-free survival, and safety.

Patient-Reported Outcome Instruments

Patients with RET-mutant MTC enrolled to LIBRETTO-001 completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3.0 at baseline (cycle 1, day 1, prior to study treatment) and approximately every 8 weeks thereafter, corresponding to imaging assessments (approximately every other cycle) until cycle 13. The QLQ-C30 questionnaire is a commonly used scale in clinical trial research worldwide and has been extensively validated and translated to more than 100 languages. It includes five functional domains (physical, role, cognitive, emotional, and social), three symptom domains (fatigue, pain, and nausea and vomiting), and six single-item symptom scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial impact) [14]. All QLQ-C30 subscales are scored from 0 to 100. Higher scores on the global health status/quality of life (QoL) and functional subscales represent better functioning. Lower scores on the symptom subscales represent fewer symptoms.

A change in global health status/QoL or functional subscale score was considered an improvement if increased from baseline by 10 or more points and considered a worsening if decreased from baseline by 10 or more points. Conversely, a decrease from baseline of 10 or more points in symptom subscale score was considered an improvement, and an increase from baseline of 10 or more points in symptom subscale score was considered a worsening [15]. Patients who met the threshold for either improvement or worsening in change from baseline subscale score, without further changes of 10 or more points reversing that change, were considered to have definite improvement or definite worsening, respectively. Mean subscale scores at each scheduled visit were evaluated in the context of previously published thresholds considered clinically meaningful to patients [16]. Functional subscale values lower than the established thresholds were considered clinically meaningful: physical function scores <83, emotional function <71, role function <58, cognitive function <75, and social function <58. Conversely, symptom subscale values higher than the established thresholds were considered clinically meaningful: fatigue score >39, pain >25, diarrhea >17, dyspnea >17, appetite loss >50, insomnia >50, constipation >50, and financial difficulties >1.

English-speaking patients with RET-mutant MTC also completed a modified version of the Systemic Therapy–Induced Diarrhea Assessment Tool (mSTIDAT) at baseline (cycle 1, day 1, prior to study treatment), weekly during cycle 1, and on day 1 of every cycle until the end of treatment. The mSTIDAT assesses the patient's perception of diarrhea, daily number of bowel movements, daily number of diarrhea episodes, diarrhea severity, the presence of urgency, abdominal discomfort, fecal incontinence, and QoL [17]. The global health status/QoL subscale (items 7 to 11 of the mSTIDAT) asks patients to rank the impact of bowel habits (items 7 to 9) and diarrhea (items 10 to 11) on their daily living, from 0 (no impact) to 10 (extreme impact). Thus, higher scores reflect a greater impact on daily living. The instrument was modified by removing the item evaluating concomitant medication use, as these data were collected elsewhere in the study.

Statistical Analysis

Compliance to each instrument was calculated as the total number of patients who completed the QLQ-C30 or mSTIDAT, divided by the total number of patients who were on treatment at each visit. Each subscale on the QLQ-C30 and each item on the mSTIDAT was reported descriptively (mean ± SD) at each assessment time point. The proportion of patients who met the criteria for improvement or worsening on each QLQ-C30 subscale (±10 or more points from baseline) were reported at each cycle among those with both baseline scores and scores at the given cycle. The proportion of patients who met the criteria for definite improvement or definite worsening (±10 or more points from baseline without reversal of that change), was also reported for each subscale of the QLQ-C30. Time to first improvement or worsening on the QLQ-C30 was evaluated using the Kaplan Meier method among patients with at least 6 months of follow-up; of note, patients with events prior to this time point were not excluded from the analysis. Subgroups evaluated included patients categorized into one of two prespecified cohorts of patients with measurable disease: those with no prior exposure to vandetanib and/or cabozantinib (V/C) at enrollment (V/C-naïve) or patients with prior exposure to either drug at enrollment (previous V/C). Data were evaluated through cycle 13, as few patients had yet reached later time points at the time of this interim analysis.

Results

Baseline characteristics of all evaluable patients with RET-mutant MTC enrolled to LIBRETTO-001 as of December 2019 are summarized in Table 1. Of these patients, 88 (41.5%) were V/C-naïve, and 124 (58.5%) had previously received these MKIs (previous V/C) at study entry. Compliance to instrument completion was greater than 85% at all scheduled study visits for both the QLQ-C30 and mSTIDAT. The number of patients evaluated was lower at each postbaseline time point because of limited follow-up at the time of this interim analysis; 83.1% of patients enrolled to LIBRETTO-001 remain on study, and patient-reported outcome data continue to be collected.

Table 1. Baseline characteristics of patients with RET-mutant MTC enrolled to LIBRETTO-001 Characteristic All patients with MTC (n = 226)a V/C-naïve patients (n = 88)b Patients with previous V/C treatment (n = 124)b Age, median (range), years 58 (15–90) 58 (15–82) 57.5 (17–90) Sex, n (%) Male 148 (65.5) 58 (65.9) 81 (65.3) Female 78 (34.5) 30 (34.1) 43 (34.7) Race, n (%) White 200 (88.5) 75 (85.2) 111 (89.5) Asian 6 (2.7) 4 (4.5) 1 (0.8) Black or African American 2 (0.9) 0 (0.0) 2 (1.6) Other 18 (8.0) 8 (9.1) 10 (8.1) ECOG performance status, n (%) 0 82 (36.3) 43 (48.9) 31 (25.0) 1 132 (58.4) 42 (47.7) 84 (67.7) 2 12 (5.3) 3 (3.4) 9 (7.3) Prior systemic therapy, n (%) Yes 148 (65.5) 16 (8.2) 124 (100.0) No 78 (34.5) 82 (81.8) 0 (0.0) Type of previous systemic therapy,c n (%) MKIs 138 (61.1) 7 (8.0) 124 (100.0) Vandetanib 99 (43.8) 0 (0.0) 96 (77.4) Cabozantinib 77 (34.1) 0 (0.0) 72 (58.1) Lenvatinib 13 (4.4) 1 (1.1) 12 (9.7) Sorafenib 10 (4.4) 4 (4.5) 6 (4.8) Other MKI 18 (8.0) 2 (2.3) 16 (12.9) Chemotherapy 18 (8.0) 3 (3.4) 15 (12.1) Platinum-containing chemotherapy 5 (2.2) 3 (3.4) 2 (1.6) Taxane-containing chemotherapy 4 (1.8) 1 (1.1) 3 (2.4) PD-1/PD-L1 inhibitors 13 (5.8) 2 (2.3) 11 (8.9) Radioiodine therapy 2 (0.9) 1 (1.1) 0 (0.0) Selective RET inhibitors 0 (0.0) 0 (0.0) 0 (0.0) Other systemic therapy 24 (10.6) 6 (6.8) 18 (14.5) Number of previous systemic therapies, n (%) 0 78 (34.5) 72 (81.8) 0 (0.0) 1–2 111 (49.1) 16 (18.2) 88 (71.0) 3 or more 37 (16.4) 0 (0.0) 36 (29.0) RET mutation, n (%) M918T 136 (60.2) 49 (55.7) 78 (62.9) Extracellular cysteine mutation 43 (19.0) 20 (22.7) 19 (15.3) V804M/L 13 (5.8) 6 (6.8) 7 (5.6) Other mutation 34 (15.0) 13 (14.8) 20 (18.2) a The overall MTC population includes an additional 14 patients with nonmeasurable disease at baseline who were not categorized into either MKI subgroup. Among these patients, seven received prior MKI therapy (five, cabozantinib; three, vandetanib), and six were naïve to systemic treatment. b Both MKI subgroups were prespecified cohorts. All patients had measurable disease with the exception of four patients (two patients in each MKI subgroup had nonmeasurable disease). c Patients could have received more than one prior treatment, and therefore the sum of percentages may be >100%. Abbreviations: ECOG, Eastern Cooperative Oncology Group; MKI, multikinase inhibitor; MTC, medullary thyroid cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; RET, rearranged during transfection; V/C, vandetanib and/or cabozantinib. QLQ-C30 Physical Function and Global Health Status/Quality of Life Subscales

Mean ± SD baseline physical function subscale scores were 80.9 ± 20.0 overall and were 85.2 ± 18.2 for patients who were V/C-naïve and 75.4 ± 21.9 for patients with previous V/C. All of these baseline values met a clinically meaningful threshold for reduced physical function (below a score of 83). Most patients improved or remained stable on the physical function subscale at each cycle during study treatment with selpercatinib (Fig. 1). Of all patients, 18.7% (36/193) met the criteria for a definite improvement, and 13.0% (25/193) met the criteria for definite worsening in physical function. Among the V/C-naïve and previous V/C subgroups, respectively, 10.5% and 22.5% met the criteria for definite improvement, and 14.5% and 11.3% met the criteria for definite worsening in physical function. Neither the median time to first improvement nor time to first worsening in physical function was reached in either the V/C-naïve or previous V/C subgroup.

Change in physical function from baseline by cycle of study treatment as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 version 3.0 in patients with RET-mutant MTC. For each respective cycle, the percentage of patients whose status improved (yellow bar), remained stable (blue bar), or worsened (green bar) from baseline was calculated using the number of patients with both baseline and corresponding postbaseline assessment as the denominator.

Abbreviations: MTC, medullary thyroid cancer; V/C, vandetanib and/or cabozantinib.

Mean ± SD baseline global health status/QoL subscale scores were 65.1 ± 23.8 overall and were 68.5 ± 23.7 and 60.6 ± 23.5 for patients who were V/C-naïve to or previously treated with V/C, respectively. Most patients improved or remained stable on the global health status/QoL subscale at each cycle during study treatment with selpercatinib (Fig. 2). Of all patients, 29.0% (56/193) met the criteria for a definite improvement in global health status/QoL, and 13.0% (25/193) met the criteria for definite worsening in global health status/QoL. Among the V/C-naïve and previous V/C subgroups, respectively, 26.3% and 31.3% met the criteria for definite improvement, and 17.1% and 12.5% met the criteria for definite worsening in global health status/QoL. The median time to first improvement was 5.6 months (95% CI, 3.7–not reached) for those in the V/C-naïve subgroup and 3.6 months (95% CI, 2.0–7.4) for patients with previous V/C exposure. Median time to first worsening was not reached in V/C-naïve patients. For patients previously treated with V/C, median time to first worsening was 11.1 months (3.8–not reached).

Change in global health status/quality of life from baseline by cycle of study treatment as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 version 3.0 in patients with RET-mutant MTC. For each respective cycle, the percentage of patients whose status improved (yellow bar), remained stable (blue bar), or worsened (green bar) from baseline was calculated using the number of patients with both baseline and corresponding postbaseline assessment as the denominator.

Abbreviations: MTC, medullary thyroid cancer; V/C, vandetanib and/or cabozantinib.

QLQ-C30 Other Functional Subscales

No other baseline functional subscales met a clinically important threshold; all functional subscale data by cycle of therapy are included in supplemental online Table 1.

QLQ-C30 Diarrhea, Appetite Loss, and Constipation Subscales

Mean ± SD baseline diarrhea subscale score was 40.1 ± 38.2 for the overall RET-mutant MTC cohort. Among patients who were V/C-naïve and for those with previous V/C exposure, mean baseline diarrhea scores were 40.8 ± 37.6 and 40.5 ± 36.9, respectively. All of these baseline values met a clinically meaningful threshold (scores were all greater than 17). Most patients' diarrhea improved or remained stable at each cycle during study treatment with selpercatinib (Fig. 3). Of all patients, 43.5% (84/193) met the criteria for definite improvement in diarrhea, and 9.8% (19/193) met the criteria for definite worsening in diarrhea. Among the V/C-naïve and previous V/C subgroups, respectively, 36.8% and 51.3% met the criteria for definite improvement, and 11.8% and 7.5% met the criteria for definite worsening in diarrhea. Median time to first improvement was 2.6 months (95% CI, 1.9–not reached) in the V/C-naïve subgroup, and was 2.0 months (95% CI, 1.9–5.6) among those with previous V/C exposure. Median time to first worsening was not met in either subgroup.

Change in diarrhea from baseline by cycle of study treatment as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 version 3.0 in patients with RET-mutant MTC. For each respective cycle, the percentage of patients whose status improved (yellow bar), remained stable (blue bar), or worsened (green bar) from baseline was calculated using the number of patients with both baseline and corresponding postbaseline assessment as the denominator.

Abbreviations: MTC, medullary thyroid cancer; V/C, vandetanib and/or cabozantinib.

Mean ± SD baseline appetite loss subscale scores were 19.7 ± 29.3 in the overall RET-mutant MTC cohort and were 15.8 ± 27.5 and 25.8 ± 30.9 among patients who were V/C-naïve and who received previous V/C, respectively (supplemental online Table 2). None of these values met the threshold of >50 for clinical importance. Of all patients, 23.3% (45/193) met the criteria for definite improvement in appetite loss, and 14.0% (27/193) met the criteria for definite worsening in appetite loss. Among the V/C-naïve and previous V/C subgroups, respectively, 15.8% and 32.5% met the criteria for definite improvement and, 17.1% and 13.8% met the criteria for definite worsening in appetite loss. Neither median time to first improvement nor time to first worsening was met in either subgroup.

Mean ± SD baseline constipation subscale score was 8.1 ± 20.3 for the overall RET-mutant MTC cohort. Among patients who were V/C-naïve and who received previous V/C, baseline constipation scores were 5.7 ± 15.8 and 9.6 ± 23.3, respectively (supplemental online Table 2). The threshold of >50 for clinical importance was not met in any cohort. Of all patients, 9.3% (18/193) met the criteria for definite improvement in constipation, and 17.1% (33/193) met the criteria for definite worsening in constipation. Among the V/C-naïve and previous V/C subgroups, respectively, 6.6% and 10.0% met the criteria for definite improvement, and 19.7% and 15.0% met the criteria for definite worsening in constipation. Median time to first improvement was not met in either subgroup. Median time to first worsening was not met in the VC-naïve subgroup but was 11.0 months (95% CI, 3.8–not reached) among those with previous V/C exposure.

QLQ-C30 Other Symptom Subscales

All other QLQ-C30 symptom subscale data are provided by cycle of therapy in supplemental online Table 2. The majority of patients reported improvements or remained stable on each subscale at all subsequent assessments overall and in both the V/C-naïve and previous V/C exposure subgroup.

mSTIDAT Diarrhea

Of the 123 English-speaking patients who competed the mSTIDAT at baseline (cycle 1), 99 (80.4%) reported experiencing diarrhea at study entry. The patient-reported severity of diarrhea at baseline was minimal among 22 (22.2%), moderate among 48 (48.5%), and severe among 25 (25.3%) patients reporting diarrhea. The patient-reported prevalence and severity of diarrhea by study cycle is summarized in Figure 4. Less than half of all patients reported diarrhea at each assessment after cycle 2 (range: 33.3%–48.3%) of treatment, with fewer patients than at baseline (range: 0%–17.2%) reporting the severity to be severe.

Prevalence of diarrhea (line graph) and proportion of patients with diarrhea who report it as severe (bar graph) as measured by the modified Systemic Therapy–Induced Diarrhea Assessment Tool.

The impact of diarrhea reported on the mSTIDAT (ranging from 0: no impact to 10: extreme impact) on family life, social life, and overall quality of life is summarized in Figure 5. At baseline, the mean ± SD impact of diarrhea was 2.7 ± 3.0 for family life, 3.6 ± 3.2 for social life, and 3.5 ± 2.8 for overall quality of life. Patients reported little impact of diarrhea on any of these aspects of daily living during study treatment with selpercatinib.

Impact of diarrhea on family life, social life, and quality of life as measured by the modified Systemic Therapy–Induced Diarrhea Assessment Tool. [a], Number of patients in the categories of family life (122), social life (122), and overall QoL (121). [b], Number of patients in the categories of family life (105), social life (104), and overall QoL (104).

Abbreviation: QoL, quality of life.

Discussion

Patients with MTC frequently experience diarrhea related to their disease, which can significantly impair daily living [18]. In this study, patient-reported diarrhea and its severity both showed improvements at each postbaseline assessment during treatment with selpercatinib on two different instruments (QLQ-C30 and mSTIDAT). The majority of patients experienced stable or improved outcomes on all functional and symptom subscales recorded in this study (supplemental online Tables 1 and 2).

The experience of patients during systemic treatment typically does not show improvement in these symptoms, which is due either to treatment or to disease factors. Meta-analyses have shown an increased risk of diarrhea with MKI treatment [19]. In this meta-analysis, the pooled overall risk of diarrhea during treatment among patients with thyroid cancer was 61.0% (95% CI, 51.2%–70.7%). In this study of patients enrolled to LIBRETTO-001, the prevalence of diarrhea during study treatment ranged from 33.3% to 48.3% at postbaseline study visits. This difference is likely associated with both the high overall response rate (69% among those with prior MKIs and 73% for those who were MKI-naïve) and high biochemical response rates (91% calcitonin biochemical response) observed in LIBRETTO-001, which may reduce the disease-related symptoms patients experience [8]. Moreover, the toxicity profile of selpercatinib, associated with only 6% grade 3–4 diarrhea during the study, is a likely contributing factor to the relatively low rates of diarrhea experienced by patients while enrolled in the study [8]. Although we cannot directly attribute the changes in disease-related symptoms or improvement in diarrhea to the effects of selpercatinib, it is important to note that at each follow-up assessment, more than 80% of patients reported improvement or stable impact on appetite loss, and less than 20% reported a worsening of constipation from baseline. The relationship between patient-reported and clinical outcomes should be further explored as the data from LIBRETTO-001 mature.

The limitations of this work include the single-arm design of the LIBRETTO-001 trial. Because of the lack of a comparator arm, one cannot infer that these results are caused by or due to selpercatinib treatment. However, it should be noted that few patients experienced worsening in any of the subscales collected in this study as summarized in supplemental online Tables 1 and 2. This work is also limited by the inconsistent collection of the QLQ-C30. As the instrument was timed to imaging rather than treatment cycles, some of the data were collected at interim time points, which reduces the number of evaluations on the odd-cycled visits. Although this represents a small proportion of the study cohort (more than 85% of all patients recorded their data on the odd-numbered visits), this does inevitably lead to a small loss of data in this study. Lastly, time-to-event outcomes evaluated on the QLQ-C30 were also limited by the infrequent data collection (approximately every 8 weeks). Since events were not recorded more frequently, the time-to-event analyses would not capture any improvement or worsening that may have occurred between assessments, resulting in a simplified statistic that may miss the nuances of the patient experience during the 8-week data gaps. Lastly, these findings are from an interim analysis of an ongoing trial. The number of patients evaluable as cycles of therapy progress sequentially decreases, as patients remain on study and have not yet reached the later cycles of treatment. Therefore, the stability of the data may be less reliable as the number of evaluable patients decreases. As the study data mature, a longer follow-up period for patients will help provide stronger evidence of patient-reported outcomes while on treatment. To, in part, address this limitation, the present time-to-event outcome analyses were restricted to patients with at least 6 months of follow-up to reduce the early censoring. Future studies will no longer require this restriction as patients continue to be treated with selpercatinib in LIBRETTO-001.

Despite the limitations of an ongoing single-arm trial, this study demonstrates how patients receiving selpercatinib perceive their own outcomes during treatment. These patient-reported outcomes are favorable, with the majority of patients experiencing improvements or stable outcomes at each assessment versus their own baseline values. This evidence further supports the favorable toxicity profile of selpercatinib treatment among patients with advanced MTC.

Conclusion

Although causality cannot be inferred because of the single-arm, noncomparative nature of this trial, the results of this interim analysis demonstrate that patients with RET-mutant MTC improved or remained stable on all domains of health-related QoL during treatment with selpercatinib. This study is based on an interim analysis of the ongoing LIBRETTO-001 trial. Future analyses will be conducted as the data mature and will be supplemented by QoL data from the ongoing phase III, confirmatory trial (LIBRETTO-531).

Acknowledgments

We thank the patients, their caregivers, and the trial teams at the participating centers, and we thank Karen Paulsrud, R.Ph. (Eli Lilly & Co.) for copyediting, editorial, and production assistance. Funding for this work was supported by Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly & Co. C.M. is currently affiliated with UCSF.

Author Contributions

Conception/design: Lori J. Wirth, Bruce Robinson, Lisa Hess, Min-Hua Jen, Elizabeth Olek, Vivek Subbiah

Provision of study material or patients: Lori J. Wirth, Bruce Robinson, Valentina Boni, Daniel S.W. Tan, Caroline McCoach, Erminia Massarelli, Vivek Subbiah

Collection and/or assembly of data: Lori J. Wirth, Bruce Robinson, Valentina Boni, Daniel S.W. Tan, Caroline McCoach, Erminia Massarelli, Elizabeth Olek

Data analysis and interpretation: Lori J. Wirth, Valentina Boni, Daniel S.W. Tan, Caroline McCoach, Erminia Massarelli, Lisa Hess, Min-Hua Jen, Jennifer Kherani, Vivek Subbiah

Manuscript writing: Lori J. Wirth, Bruce Robinson, Valentina Boni, Daniel S.W. Tan, Caroline McCoach, Erminia Massarelli, Lisa M. Hess, Min-Hua Jen, Jennifer Kherani, Elizabeth Olek, Vivek Subbiah

Final approval of manuscript: Lori J. Wirth, Bruce Robinson, Valentina Boni, Daniel S.W. Tan, Caroline McCoach, Erminia Massarelli, Lisa M. Hess, Min-Hua Jen, Jennifer Kherani, Elizabeth Olek, Vivek Subbiah

Disclosures

Lori J. Wirth: Ayala Pharmaceuticals, Bayer HealthCare Pharmaceuticals Inc., Blueprint Medicines, Cue Biopharma, Cullinan Oncology, Eisai Inc., Eli Lilly & Co., Genentech USA, Inc., Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly & Co., Merck, NewLink Genetics Corp., Novartis, Rakuten Medical (SAB, C/A), Eli Lilly & Co. (other—steering committee), Iovance Biotherapeutics (other—Data Safety Monitoring Board); Bruce Robinson: Eisai, Eli Lilly & Co. (C/A); Valentina Boni: Puma Biotechnology, Ideaya Biosciences, Loxo Therapeutics, CytomX Therapeutics, Guidepoint, Oncoart, Amunix (C/A), Abbvie, ACEO, Adaptaimmune, Amcure, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytomx, GlaxoSmithKline, Genentech/Roche, H3, Incyte, Janssen, Kura, Eli Lilly & Co., Loxo, Nektar, Macrogenics, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, PUMA, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Takeda, Incyte, Innovio, Merck Sharp & Dohme, PsiOxus, Seattle Genetics, Mersana, Daiichi, Nektar, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharm, Boehringen Ingelheim, Regeneron, Millenium, Synthon, Spectrum, Rigontec, Zenith (RF); Daniel S. W. Tan: Novartis, Merck, AstraZeneca, Roche, Pfizer, Bayer, Amgen (C/A), Bristol-Myers Squibb, Takeda, Novartis, Roche, Pfizer, Merck Sharp & Dohme (H), Novartis, GlaxoSmithKline, AstraZeneca (RF); Caroline McCoach: Genentech, AstraZeneca (C/A), Novartis, Guardant Health (H), Novartis, Revolution Medicines (RF), Genentech (E); Erminia Massarelli: Merck, Janssen (C/A), Merck, AstraZeneca, Eli Lilly & Co. (H); Lisa M. Hess: Eli Lilly & Co (E, OI); Min-Hua Jen: Eli Lilly & Co (E, OI); Jennifer Kherani: Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly & Co. (E, OI); Elizabeth Olek: Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly & Co. (E, OI); Vivek Subbiah: Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly & Co. (RF, C/A, SAB), Roche/Genentech, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Altum, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, NCI-CTEP, UT MD Anderson Cancer Center, Turning Point Therapeutics, Boston Pharmaceuticals, Novartis, Pharmamar, Medimmune (RF—outside of this work), Helsinn, Incyte, QED Pharma, Daiichi-Sankyo, Signant Health, Novartis, Medimmune (C/A), Pharmamar, Incyte, ASCO (other—travel), Medscape (other—CME preparation).

(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board

See http://www.TheOncologist.com for supplemental material available online.

Filename Description onco13977-sup-0001-TableS1.pdfPDF document, 355.5 KB

Table S1 EORTC QLQ-C30 global health status/QoL and function subscale scores by cycle in patients with RET-mutant MTC

Table S2. EORTC QLQ-C30 symptom subscale scores by cycle in patients with RET-mutant MTC

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