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ESMO 2020: Late-breaking and practice-changing studies

Thursday, October 1, 2020

There were a number of practice-changing and ground-breaking studies presented at the ESMO 2020 Virtual Congress, according to our guest in this episode.

Alan P. Lyss, MD, subprincipal investigator for Heartland Cancer Research NCORP, joined host David H. Henry, MD, to review highlights from ESMO 2020.

The pair discussed studies on gynecologic, breast, lung, gastrointestinal, and genitourinary cancers, as well as studies of anemia and COVID-19 in cancer patients.

COVID-19 and cancer

LBA77: Anti-SARS-CoV-2 antibody response in patients with cancer and oncology healthcare workers: A multicenter, prospective study. https://bit.ly/3cNNkar

  • This study suggests SARS-CoV-2-specific IgG antibody response is not different between cancer patients (n = 61) and subjects without cancer (n = 105).
  • Overall, 83.8% of subjects were IgG-positive, and there was no significant difference in IgG positivity between the cancer patients and the health care workers (P = .39).


LBA83: Outcomes of the 2019 novel coronavirus in patients with or without a history of cancer: A multi-centre North London experience. https://bit.ly/2EJMpv4

  • This study suggests COVID-19 patients with a history of cancer may have a similar risk of death as COVID patients without a history of cancer, with exceptions.
  • The odds ratio for mortality, comparing the cancer patients (n = 30) to the non-cancer patients (n = 90), was 1.05.
  • The odds ratio for mortality was 4.05 for cancer patients who had received systemic therapy in the prior 28 days.

Lung cancer: Radiotherapy

LBA3_PR: An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: Primary end-point analysis of LungART (IFCT-0503, UK NCRI, SAKK) NCT00410683. https://bit.ly/3jtojUo

  • This study enrolled 501 patients with completely resected NSCLC and mediastinal N2 involvement, and they were randomized to PORT or no PORT.
  • There was no significant between-arm difference in disease-free survival (DFS) or overall survival (OS).
  • The 3-year DFS rate was 47.1% with PORT and 43.8% with no PORT. The 3-year OS rate was 66.5% and 68.5%, respectively.
  • These results suggest conformal PORT should not be standard care in all completely resected N2 NSCLC patients, according to Dr. Lyss. “This may have been the most obviously and immediately practice-changing study among those I heard presented,” he said.

Endometrial cancer

LBA28: A randomised double-blind placebo-controlled phase II trial of palbociclib combined with letrozole (L) in patients (pts) with oestrogen receptor-positive (ER+) advanced/recurrent endometrial cancer (EC): NSGO-PALEO / ENGOT-EN3 trial. https://bit.ly/2SanTX1

  • This study enrolled 77 patients with ER+ advanced or recurrent endometrial cancer, and they were randomized to palbociclib plus letrozole or placebo plus letrozole.
  • The median progression-free survival (PFS) was 8.3 months in the palbociclib arm and 3 months in the control arm.
  • Dr. Lyss called this a “small” but “important” study. He and Dr. Henry agreed that a confirmatory study is needed.

Breast cancer

LBA5_PR: Abemaciclib in high risk early breast cancer. https://bit.ly/3igxbvw

  • This trial enrolled 5,637 women with hormone receptor-positive, HER2/neu oncogene-negative, early breast cancer.
  • They were randomized to receive standard endocrine therapy (ET) alone or standard ET with abemaciclib.
  • The 2-year invasive DFS rate was 92.2% with abemaciclib and 88.7% with ET alone (hazard ratio, 0.747; P = .0096).
  • Dr. Lyss said these data suggest abemaciclib could have “the potential to save many thousands of lives.”
  • However, he noted that 16% of patients discontinued abemaciclib prematurely due to adverse events, and more than 300 of the 463 patients who stopped abemaciclib also stopped ET – a “disaster,” according to Dr. Lyss.

LBA12: PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer. https://bit.ly/2GbuluE

  • This trial enrolled 5,760 patients with hormone receptor-positive/HER2-negative early stage breast cancer. They were randomized to palbociclib plus ET or ET alone.
  • Results from this trial run counter to results from the abemaciclib trial, in that adding palbociclib to ET did not improve invasive DFS.
  • The 3-year invasive DFS rate was 88.2% in the palbociclib arm and 88.5% in the ET-alone arm (HR, 0.93).
  • Dr. Lyss said he can see no explanation for the different results with abemaciclib and palbociclib, but longer follow-up and analyses of biospecimens may shed some light.

LBA17: ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). https://bit.ly/3ilHwGd

  • The study enrolled 529 patients with relapsed/refractory metastatic TNBC.
  • They were randomized to SG or single-agent physician’s choice of therapy (capecitabine, eribulin, vinorelbine, or gemcitabine).
  • SG outperformed physician's choice. The median PFS was 5.6 months with SG and 1.7 months with physician’s choice. The median OS was 12.1 months and 6.7 months, respectively.


LBA16: IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. https://bit.ly/33fYYb7

  • This trial enrolled 902 patients with locally advanced or metastatic TNBC.
  • They were randomized to first-line nab-paclitaxel plus placebo or nab-paclitaxel plus atezolizumab.
  • The median OS was 21 months in the atezolizumab arm and 18.7 months in the control arm (HR, 0.87, P = .0770).
  • The 3-year OS in PD-L1-positive patients was 36% and 22%, respectively. “I think anybody would choose the combination with atezolizumab with a difference like that,” Dr. Lyss said.


LBA15: Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). https://bit.ly/36iEoIS

  • This trial enrolled 651 patients with locally advanced or metastatic TNBC.
  • They were randomized to first-line paclitaxel plus placebo or paclitaxel plus atezolizumab.
  • Dr. Lyss noted that, unlike IMpassion130, the results of IMpassion131 were “completely negative.”
  • In the PD-L1-positive population, the median PFS was 5.7 months in the placebo arm and 6.0 months in the atezolizumab arm (HR, 0.82; P = .20).
  • In the overall population, the median PFS was 5.6 months and 5.7 months, respectively (HR, 0.86).
  • It’s unclear why results from IMpassion130 and IMpassion131 differ, Dr. Henry noted. Steroid use, study design, or chance might all play a role, according to a discussant at ESMO.

Urothelial cancer

LBA24: TROPHY-U-01 cohort 1 final results: A phase II study of sacituzumab govitecan (SG) in metastatic urothelial cancer (mUC) that has progressed after platinum (PLT) and checkpoint inhibitors (CPI). https://bit.ly/3kYvq7R

  • This study enrolled 113 patients with unresectable locally advanced or metastatic urothelial cancer. All patients received SG.
  • The overall response rate was 27% in the overall population and 25% in patients with liver metastasis.
  • The median PFS was 5.4 months, and the median OS was 10.5 months.
  • Dr. Henry said the response and survival data were “rather impressive,” and Dr. Lyss noted that biomarker studies might allow for better selection of patients who should receive SG.

Gastrointestinal cancer

LBA6_PR: Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. https://bit.ly/2GcOroj

  • This study enrolled 1,581 patients with GC, GEJC, or EAC, and 60% of patients were PD-L1-positive with a combined positive score (CPS) of at least 5.
  • Patients were randomized to first-line treatment with nivolumab plus chemotherapy or chemotherapy alone (XELOX or FOLFOX).
  • In patients with PD-L1 CPS ≥ 5, the median OS was 14.4 months in the nivolumab arm and 11.1 months in the chemotherapy arm (HR, 0.71; P < .0001).
  • The median PFS was 7.7 months and 6.2 months, respectively (HR, 0.68; P < .0001).
  • Dr. Lyss noted that using checkpoint inhibitors in the frontline or even adjuvant setting appears beneficial in this patient population, as demonstrated by additional trials presented at ESMO 2020:

Lung cancer: Checkpoint inhibitors

Dr. Henry briefly discussed three abstracts on checkpoint inhibitors in NSCLC — LBA51, LBA52, and LBA53.

LBA51: KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%. https://bit.ly/2ELdNsE

  • The 5-year OS rate was 31.9% with pembrolizumab and 16.3% with chemotherapy (HR, 0.62).

LBA52: EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. https://bit.ly/3jjSiy9

  • The median OS was 22.1 months in the cemiplimab arm and 14.3 months in the chemotherapy arm (P = .002).

LBA53: Precision immuno-oncology for advanced non-small cell lung cancer (NSCLC) patients (pts) treated with PD1/L1 immune checkpoint inhibitors (ICIs): A first analysis of the PIONeeR study. https://bit.ly/2GbjhO0

  • This study revealed biomarkers that might help guide treatment with immune checkpoint inhibitors.

Renal cell carcinoma

696O_PR: Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial. https://bit.ly/30lEMmg

  • This study enrolled 651 patients with previously untreated metastatic renal cancer.
  • They were randomized to cabozantinib plus nivolumab or sunitinib.
  • The median PFS was 16.6 months with the combination and 8.3 months with sunitinib.
  • The median OS was improved with the combination as well (HR, 0.61).
  • Dr. Lyss said these results support the use of nivolumab plus cabozantinib in this patient population. However, he also expressed reservations related to tolerability, quality of life, eligibility criteria, and short follow-up.

Anemia

1822P: Impact of iron-deficiency management on quality of life in cancer patients: A prospective cohort study (CAMARA study). https://bit.ly/2Sf1TdE

  • This study enrolled 248 patients with solid tumors, including 74.5% with absolute iron deficiency (transferrin saturation coefficient < 20%) and 191 with anemia.
  • Patients were treated with intravenous iron, and their quality of life (FACT-An scores) improved significantly between study enrollment and each assessment.
  • Dr. Henry said the take-home message is that clinicians shouldn’t miss anemia or iron deficiency, and they shouldn’t transfuse patients automatically but, instead, consider iron supplementation.

Disclosures:

Dr. Henry has no financial disclosures relevant to this episode.

Dr. Lyss writes a column for MDedge Hematology/Oncology called Clinical Insights. He has no other conflicts of interest.


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Podcast Participants

David Henry, MD
David Henry, MD, FACP, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He received his bachelor’s degree from Princeton University and his MD from the University of Pennsylvania, then completed his internship, residency, and fellowship at the Hospital of the University of Pennsylvania. After 2 years as an attending in the U.S. Air Force, he was drawn to practicing as a hem-onc because of the close patient contact and interaction, and his belief that, win or lose with each patient, one can always make a difference in their care and lives. Follow Dr. Henry on Twitter: @davidhenrymd. Dr. Henry reported being on the advisory board for Amgen, AMAG Pharmaceuticals, and Pharmacosmos. He reported institutional funding from the National Institutes of Health and FibroGen.