Clinical Highlights from the First Virtual European Society for Medical Oncology Congress
December 11, 2020
This year’s ESMO Annual Scientific Meeting took place between 19th-21st of September, with the Educational Program occurring during the 16th-18th of October and an extended virtual exhibition of presented materials being available between September 14 and October 18. In contrast to all previous years, when scientists, clinicians, cancer nurses, industry partners, patient advocates and relevant press and media gathered in the warm city of Barcelona, in Spain, this year’s meeting took place virtually, with a comprehensive congress schedule and all other necessary resources being accessible online. ESMO managed to create the perfect platform for sharing the most recent discoveries and ongoing studies of the field in over 2,100 oral presentations and posters. The focus of this year’s meeting was on (immuno)oncology developments in breast cancer, non-small cell lung cancer (NSCLC) and gastrointestinal (GI) cancers. The scientific program also included a dedicated COVID-19 and cancer research track. Selected high-impact news and information are summarized below.
The evolving landscape of breast cancer therapies
Immune checkpoint inhibitors in triple-negative breast cancer (TNBC)
The first immune checkpoint inhibitor approved for metastatic programmed cell death protein ligand 1 (PD-L1)-positive TNBC was atezolizumab (Tecentriq, Roche) in combination with protein-bound paclitaxel (Abraxane, Celgene), which gained approval in 2019 based on the positive progression-free survival (PFS) data from the Phase 3 IMPASSION130 trial (7.4 vs 4.8 months after atezolizumab and nab-paclitaxel vs placebo and nab-paclitaxel treatment). Continued approval for TNBC was contingent on verification of clinical benefit by assessment of overall survival (OS) data in the PD-L1-positive population of the same trial, which was presented at ESMO 2020 (24.5 vs 17.9 months for the atezolizumab and nab-paclitaxel vs placebo and nab-paclitaxel arms; Abstract LBA16). Controversially, data from the confirmatory Phase 3 trial IMPASSION131 revealed no difference between patients with metastatic TNBC who received atezolizumab and paclitaxel vs placebo and paclitaxel in terms of PFS and OS, irrespective of PD-L1 status (Abstract LBA15). Furthermore, data presented earlier this year at ASCO 2020 on another immune checkpoint inhibitor reported a statistically significant improvement in median PFS for inoperable/metastatic PD-L1-positive TNBC following pembrolizumab (Keytruda, Merck) plus nab-paclitaxel treatment vs placebo plus nab- paclitaxel (9.7 vs 5.6 months; Phase 3 KEYNOTE-355 trial). While the scientific justification for these conflicting data is currently under investigation, results might influence physicians’ treatment choice for TNBC.
Cyclin-dependent kinase (CDK) 4/6 inhibitors in early-stage hormone receptor (HR)- positive / human epidermal growth factor receptor 2 (HER2)-negative breast cancer
The three CDK4/6 pioneer inhibitors palbociclib (Ibrance, Pfizer), abemaciclib (Verzenio, Eli Lilly) and ribociclib (Kisqali, Novartis) are currently the standard of care for first-line advanced/metastatic HR-positive/HER2-negative breast cancer, two of which are evaluated in early-stage disease as well. The ESMO 2020 data revealed contrasting results for these competitors.
Interim results from the Phase 3 PALLAS trial which enrolled patients with stage II-III HR- positive / HER2-negative breast cancer who received adjuvant endocrine therapy with or without palbociclib reported that the 3-year invasive disease-free survival (iDFS) was similar between treatment arms (88.2% vs 88.5%; Abstract LBA12). On the other hand, combined abemaciclib and endocrine therapy for high-risk early-stage HR-positive / HER2-negative breast cancer patients in the Phase 3 MonarchE trial resulted in a superior 2-year iDFS when compared with endocrine therapy alone (92.2% vs 88.7%) and in a 25.3% reduction in the risk of an iDFS event (Abstract LBA5). While a final explanation for this difference is not yet agreed upon, one underlying reason might be the difference in target patient populations, with abemaciclib administered to high-risk patients, more likely to derive a benefit from additional interventions. To this extent, palbociclib is currently also being investigated in high-risk patients in the Phase 3 PENELOPE-B trial.
The evolving landscape of NSCLC therapies
Recently emerging therapies for the treatment of NSCLC are the monoclonal PD-1 antibody cemiplimab (Libtayo, Regeneron Pharmaceuticals and Sanofi) and the anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) inhibitor lorlatinib (Lorbena / Lorviqua, Pfizer).
Interim results from the Phase 3 EMPOWER-Lung1 trial reported that median OS after cemiplimab monotherapy for front-line treatment of PD-L1 ≥50% tissue polypeptide specific antigen (TPS) metastatic NSCLC patients was not reached vs 14.2 months after platinum doublet chemotherapy (hazard ratio 0.57, p <0.001). Noteworthy, in April 2020, the sponsors announced early stop of the trial due to overwhelming efficacy. The safety profile of cemiplimab was found to be consistent with earlier results evaluating the compound and with those of other PD-1/PD-L1 monoclonal antibodies (Abstract LBA52), thus putting forward the expectation of regulatory filings in the United States and Europe in the near future. Nevertheless, opinions are divided regarding cemiplimab’s potential to threaten the first monotherapy approved for treatment of high PD-L1-expressing NSCLC, namely pembrolizumab (Keytruda, MSD).
The Phase 3 CROWN trial evaluated lorlatinib for first-line treatment of metastatic ALK- translocation-positive NSCLC in comparison with the current standard of care crizotinib (Xalkori, Pfizer). Results from the planned interim analysis reported better efficacy outcomes for lorlatinib vs crizotinib, with blinded independent review committee (BICR) PFS assessment revealing a 72% reduction in the risk of PFS events in the lorlatinib arm (hazard ration [HR] 0.28, p <0.001; Abstract LBA2). Median PFS was not estimable vs 9.3 months in the lolatinib vs crizotinib arms. The BICR-assessed secondary endpoint of intracranial complete response also favored lorlatinib in patients with measurable disease at baseline (71% vs 8%). While lorlatinib displays results superior to those of crizotinib, a more interesting comparison would be with the other three ALK inhibitors approved for first-line treatment of ALK-positive metastatic NSCLC in the United States and Europe, namely alectinib (Alecensa, Roche), brigatinib (Alunbrig, Takeda) and ceritinib (Zykadia, Novartis).
Immune checkpoint inhibitors in GI cancers
In the last few years, immune checkpoint inhibitors have gained increasing attention as monotherapies or combined in multiple therapies for treatment of several cancer types. Pembrolizumab (Keytruda, Merck) and nivolumab (Opdivo, BMS) are two of the frontrunners in this class.
Results from the Phase 2/3 ATTRACTION-4 and Phase 3 CheckMate-649 trials, which evaluated nivolumab plus chemotherapy vs chemotherapy alone in patients with non-HER2- positive adenocarcinoma and from the Phase 3 KEYNOTE-590 trial, which evaluated pembrolizumab plus chemotherapy vs chemotherapy alone, were presented at ESMO 2020.
While the CheckMate-649 trial met its endpoint by improving both PFS and OS (PFS: HR 0.68 [98% CI 0.56–0.81; P < 0.0001] and OS: HR 0.71 [98.4% CI 0.59–0.86; P < 0.0001]; Abstract LBA6), the ATTACTION-4 trial, which only enrolled Asian patients, showed an improvement in only one of the co-primary endpoints (PFS: HR 0.68; 98.51% CI 0.51-0.90; p=0.0007; median PFS, 10.5 vs. 8.3 months; OS: HR 0.90; 95% CI 0.75-1.08; p=0.257; median OS, 17.5 vs. 17.2 months; Abstract LBA7). The KEYNOTE-590 trial evaluating pembrolizumab reported superior PFS (median: 6.3 vs 5.8 months; HR 0.65; 95% CI, 0.55-0.76; P < 0.0001), OS (median: 12.4 vs 9.8 months; HR, 0.73, 95% CI, 0.62-0.86; P < 0.0001), and overall response rate (45.0% vs 29.3%, P < 0.0001) in locally advanced/unresectable or metastatic esophagogastric junction adenocarcinoma patients vs chemotherapy alone (Abstract LBA8). These results highlight the potential of immune checkpoint inhibitors, in combination with chemotherapy, to become the new standard of care for patients with GI cancers.
Impact of coronavirus-19 (COVID-19) on cancer
As expected, one of the main focuses of this year’s ESMO was the impact of COVID-19 on patients with cancer. Among the studies presented during the meeting, and which mostly covered emerging results at local or national level, the international TERAVOLT study stood out.
TERAVOLT: The analysis of the Thoracic cancERs internAtional coVid 19 cOLlaboraTion international registry (Abstract LBA75), containing thus far 1012 patients (82% with NSCLC) from 20 countries, revealed that 65% of patients were on treatment (of which 38% on chemotherapy, 26% on an immune checkpoint inhibitor, 16% on a tyrosine kinase inhibitor), and 56% developed complications (the most frequent being pneumonia, 40%). Of these patients, only 33% continued their oncology treatment after COVID-19 infection. The main conclusions of the study thus far highlighted the need for physicians to evaluate the risk of mortality from COVID-19 based on age, smoking status, stage of cancer, performance status, need for steroids and specific therapy, for appropriately tailoring patient care.
To conclude, while pembrolizumab and the impact of COVID-19 on cancer where mainstay topics also addressed earlier this year during ASCO 2020, the focus of this year’s ESMO was set on immuno-oncology developments in the field, and particularly immune checkpoint inhibitors as monotherapy or in combination therapies, whose relevance CATO SMS highlighted in a recent white paper.