ABSTRACT
Introduction: Stage IIIB-IV non-small cell lung cancer patients with mutations in the EGF receptor gene (EGFR) usually derive clinical benefit from to tyrosine kinase inhibitors (EGFR TKIs) but ultimately relapse. In preclinical studies, we have showed that anti-EGF antibodies generated by vaccination significantly increased the antitumor activity of TKIs in EGFR-mut cell lines, blocking EGFR, Erk1/2, Akt and STAT3 activation and delaying emergence of resistance. Based on these findings, the EPICAL trial was initiated (ClinicalTrials.gov number, NCT03623750). Methods: The EPICAL was a single arm, phase 1b, single arm study to evaluate the safety and efficacy of first line anti-EGF vaccination combined with afatinib. The trial enrolled advanced NSCLC patients with sensitizing EGFR mutations confirmed in a central laboratory. Patients received 40 mg/day of afatinib and five intramuscular anti-EGF vaccinations every 14 days and then every three months until progression. Four medical centers in Spain participated, with a target enrollment of 30 patients. However, the COVID-19 outbreak forced an early termination of the study in March 2020 with only 23 patients included. Serial blood samples were collected and used to evaluate the levels of selected growth factors by ELISA and biological activity by addition of sera to in vitro cultures of EGFR-mut cells followed by Western blotting. Results: Of the 23 patients enrolled in the trial, nine (39%) had exon 19 in-frame deletions, twelve (52%) exon 21 substitutions and two (9%) exon 18 missense mutations. Combination treatment was well tolerated and no SAES related to anti-EGF vaccination were reported. Objective response and disease control rates were 78.3% (95%CI=53.6-92.5) and 95.7% (95%CI=78.1-99.9), respectively. At data cut-off, with a median follow-up of 11.4 months (95%CI=8.1-15.2), the median progression-free survival was 17.4 months (95% CI=13.22-NA) and median survival not reached (95% CI=15.21-NA). Median PFS for patients with exon 19 deletions and exon 21 point mutations were 13.9 months (95%CI=8.7-NR) and 17.4 months (95%CI=13.2-NR), respectively. Three months after initiation of treatment, high titers of anti-EGF antibodies were detected in all patients and serum EGF and TGFα levels were found to be significantly lower compared to baseline levels. Finally, treatment with post-vaccination patient’s sera inhibited EGFR, AKT and ERK1/2 phosphorylation in EGFR-mut cells growing in vitro. Conclusion: The combination of an anti–EGF vaccine with afatinib is well tolerated and induces a sustained immunogenic effect. Vaccination against EGF might enhance the clinical efficacy of EGFR TKIs. Keywords: anti-EGF vaccination, EGFR-mutant non-small cell lung cancer, EGFR inhibitors
ABSTRACT
Background: The SARS CoV 2 coronavirus pandemic has rocked health care systems to the core. Concurrent circulation of COVID 19 has led to service disruptions and delays in the standard procedures related to lung cancer (LC) diagnose and may negatively impact in the management, care and therapeutic patient intervention. We aimed to determine COVID 19 impact in the molecular diagnosis of LC at our institution. Methods: A total of 203 patients (pts) diagnosed with advanced NSCLC with molecular testing requested in the period of 2019–2020 were included. Clinical characteristics and testing patient results evaluated in 2019 and 2020 were compared. The SOC at our institution includes evaluation of DNA and RNA from tissue(t) and/or blood(b) with NGS or nCounter. Single-gene testing by PCR, IHC and/or FISH is used as complementary assays to NGS when tissue is limited or in case of genomic platform service interruptions. Results: A total of 106 and 97 pts were required for molecular testing during 2019 and 2020 respectively. Clinical patient characteristics in both cohorts were very similar and there were no significant differences in the number of DNA-based or RNA-based analyses required between both period times (DNAt p = 0.25;DNAb p = 0.59;RNAt p =.08). The 2019 cohort identified 66 pts (65%) with driver genes: being KRAS the most commonly detected (34%), followed by EGFR 15%, BRAF 4%, ALK 4% and METΔ14 4%. During 2020, driver alterations were found in 56 pts (60%) in a quite similar proportion except for KRAS mutations, 21%. The total number of non evaluable (NE) samples was significantly increased in 2020 compared to 2019 (p =.029). During 2019, 80% of the NE samples could be evaluated by any multiplex technique. On the contrary, during 2020 only 54% of NE were tested by any NGS-based method. Conclusions: Our results show that molecular diagnosis of LC could be preserved during the COVID 19 outbreak. However genomic service disruptions during critical months of the pandemic clearly impacted in the number of pts with a NE result and might explain the differences in the incidence of KRAS mutations observed. While this global crisis rightly demands the world's attention, a continuous and accurate molecular diagnostic testing must be ensured to guarantee quality-care for LC pts. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: C. Teixido: Honoraria (self), Personal fees: Pfizer;Honoraria (self), Personal fees: Novartis;Honoraria (self), Personal fees: Takeda;Honoraria (self), Personal fees: MSD;Honoraria (self), Personal fees: Roche;Honoraria (self), Personal fees: Diaceutics;Honoraria (self), Personal fees: AstraZeneca;Research grant/Funding (self), Research funding: Pfizer;Research grant/Funding (self), Research funding: Novartis. R. Reyes: Honoraria (self), Speaker Honoraria: Roche;Honoraria (self), Speaker Honoraria: MSD. L. Mezquita: Honoraria (self), Speaker Honoraria: Bristol-Myers Squibb;Honoraria (self), Speaker Honoraria: Tecnofarma;Honoraria (self), Speaker Honoraria: Roche;Honoraria (self), Speaker Honoraria: Takeda;Advisory/Consultancy: Roche Diagnostics;Advisory/Consultancy: Takeda;Advisory/Consultancy: Roche;Travel/Accommodation/Expenses: Bristol-Myers Squibb;Travel/Accommodation/Expenses: Roche;Research grant/Funding (self): Amgen;Research grant/Funding (self): Bristol-Myers Squibb;Research grant/Funding (self): Boehringer Ingelheim;Speaker Bureau/Expert testimony, Mentorship program with key opinion leaders: AstraZeneca. N. Reguart: Honoraria (self), Speaker Honoraria: MSD;Honoraria (self), Speaker Honoraria: BMS;Honoraria (self), Speaker Honoraria: Roche;Honoraria (self), Speaker Honoraria: Boehringer Ingelheim;Honoraria (self), Speaker Honoraria: Guardant Health;Honoraria (self), Speaker Honoraria: Pfizer;Honoraria (self), Speaker Honoraria: AbbVie;Honoraria (self), Speaker Honoraria: Ipsen;Honoraria (self), Speaker Honoraria: Novartis;Honoraria (self), Speaker Honoraria: AstraZeneca;Honoraria (self), Speaker onoraria: Lilly;Honoraria (self), Speaker Honoraria: Takeda;Honoraria (self), Speaker Honoraria: Amgen;Honoraria (self), Organization of educational events: Amgen;Honoraria (self), Organization of educational events: Roche;Advisory/Consultancy: MSD;Advisory/Consultancy: BMS;Advisory/Consultancy: Roche;Advisory/Consultancy: Boehringer Ingelheim;Advisory/Consultancy: Guardant Health;Advisory/Consultancy: Pfizer;Advisory/Consultancy: AbbVie;Advisory/Consultancy: Ipsen;Advisory/Consultancy: Novartis;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Lilly;Advisory/Consultancy: Takeda;Advisory/Consultancy: Amgen;Travel/Accommodation/Expenses: Boehringer Ingelheim;Travel/Accommodation/Expenses: MSD;Travel/Accommodation/Expenses: Roche;Research grant/Funding (self): Novartis;Research grant/Funding (self): Pfizer. All other authors have declared no conflicts of interest.
ABSTRACT
Introduction: COVID-19 pandemic has drastically changed the management of patients with cancer. The prioritization of the healthcare towards COVID-19 patients could interfere with the initial diagnosis, resulting in delayed treatment and worse outcome. We aimed to study the incidence of lung cancer new diagnosis, severity and clinical outcomes during Covid-19-period (during-COVID) compared to the same period in 2019 (before-COVID). Methods: Bicenter retrospective cohort study of newly diagnosed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients before (Jan-Jun/19) and during COVID-19 (Jan-Jun/20) in Spain. Clinical data were collected. We primarily assessed the difference on new lung cancer cases between both periods, and the disease severity considering: Performance status (PS), stage and any significant complication at diagnosis. Secondarily, we assessed the 30 days-mortality rate, progression-free survival (PFS) and overall survival (OS) by period. Results: 162 newly diagnosed lung cancer patients (68% NSCLC and 32% SCLC) were enrolled, with median age of 66 years, 70% were male, 33% smokers, 25% with PS ≥2. Advanced disease was diagnosed in 50% of NSCLC and 61% SCLC;13% of NSCLC harbored driver alterations. During-COVID, the number of new cases diagnosed decreased by 38% (43 NSCLC;19 SCLC), compared to before-COVID period (67 NSCLC;33 SCLC). More symptomatic cases were new diagnosed during vs. before-COVID. The Table 1 summarized clinical data and complications of new lung cancer cases by period and histology. In NSCLC population diagnosed during-COVID, we observed more respiratory symptoms at diagnosis (30% vs. 23% before-COVID) with mainly locally-advanced/advanced disease (82% vs. 76% before-COVID). Among the cases hospitalized, the mortality during-hospitalization was 44% (2/9) vs. 17% before-COVID. In SCLC population diagnosed during-COVID, respiratory symptoms were more common (32% vs. 24% before-COVID), but no more aggressive disease observed in terms of stage, complications and hospitalizations. Among the 4 cases hospitalized at diagnosis, none died during-hospitalization vs. 18% before-COVID (2/11). Overall, during-Covid the mOS was 6.7 months [95% CI, 5.4-not reached] vs. 7.9 months [95% CI, 4.7-12] before-COVID. In NSCLC, the 30-days mortality was 49% vs. 25% before-COVID;in SCLC, it was 32% vs. 18% before-COVID. Updated data and treatment outcomes will be presented in the meeting. [Formula presented] Conclusion: Lung cancer diagnosis has been affected during the COVID-19 pandemic with fewer cases diagnosed and more symptomatic disease compared to 2019, which seems to be associated with worse outcomes. This study is still ongoing. Keywords: NSCLC, SCLC, COVID-19
ABSTRACT
Introduction: Covid-19 pandemic has drastically changed the management of patients with cancer;however, there is still limited data regarding the real impact of Covid-19 on patient’s outcomes due to delayed diagnosis and treatment of clinical complications. We aimed to assess the prevalence, severity and mortality of clinical complications and oncology emergencies in hospitalized patients in our institution during the Covid19 period vs. the same period of 2019. Methods: We conducted a retrospective study of patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) who were admitted to the Department of Medical Oncology during Jan-Jun 2019 (before-Covid) and Jan-Jun 2020 (Covid-19 period). Clinical, pathological and biological data were collected. We assessed the clinical severity in both periods including: PS at admission, progression disease (PD), oncologic emergencies (%), start of a systemic therapy or switch to other therapy line. We also analyzed the differences on the 30-day mortality rate since hospitalization between both periods. Results: 229 admissions, 133 during and 93 before Covid-19 pandemic (N=180 patients) were enrolled;the median duration of the hospitalization was 9 days (4-16). Median age was 66 years, 35% were female, 88% with PS≥2, 27% were current smokers;83% had NSCLC histology. Most of them (82%) had advanced disease at admission;69% were under systemic therapy (chemotherapy 39%, immunotherapy 17%, targeted therapies 11%). Nine patients (4%) were active covid-19 cases (9 NSCLC, 0 SCLC). The table 1 summarized the most common clinical conditions by histology, in both periods. In NSCLC population, during-Covid, lower rate of admissions were observed (4 cases less per month), with no increase of oncologic emergencies. The PD during hospitalization was slightly higher during vs. before-Covid, but no differences were observed in 30-days mortality rate. In SCLC population, during-Covid, the rate of admissions was doubled (2 cases more per month), with more cases progressing during the hospitalization. (46% during vs. 34% before-Covid). In contrast to NSCLC, the 30-days mortality rate was higher during-Covid (38%) vs. before-Covid (20%). Updated data will be presented in the meeting. [Formula presented] Conclusion: We preliminary observed more aggressive disease with worse outcomes in patients with SCLC hospitalized during-Covid compared to the same period in 2019. No differences were observed in NSCLC. The final outcomes will be assessed in a larger and mature cohort still ongoing. Keywords: lung cancer, COVID-19, hospitalization