ESMO 2018: 55 take-home messages

Breast cancer

Advanced stage:

• IMpassion130: Atezolizumab plus nab-paclitaxel improves the overall survival of patients with PD-L1 positive, triple-negative breast cancer (Schmid P et al., Abstract LBA1_PR).
• SOLAR-1: The PI3K-Inhibitor alpelisib confers a significant progression free survival advantage for patients with PI3K mutated tumors (André F et al., Abstract LBA3_PR).
• PALOMA-3: The improvement of overall survival with palbociclib is clinically relevant. CDK4/6 inhibitors continue to be definite constituents of therapy (Cristofanilli M et al., Abstract LBA2_PR).

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Early stage:

• In HOBOE-2 premenopausal patients benefit best from the combination zoledronic acid/letrozol, in terms of disease-free survival (Perrone F et al., Abstract LBA14_PR).
• CANTO: Adherence to adjuvant endocrine therapy needs to be improved, demonstrating the need for improved patient education (Pistilli B et al., Abstract 185O_PR).
• shortHER demonstrates similar disease-free survival with nine weeks vs. one year of trastuzumab treatment in low- and intermediate-risk patients (Dieci MV et al., Abstract 186O).
• PERSEPHONE: twelve months of adjuvant trastuzumab treatment remains the standard (Hulme C et al., Abstract LBA12_PR).

Cholangiocellular Carcinoma

• S-1, an oral prodrug of 5-FU in combination with gemcitabine and cisplatin is a new and feasible first-line option for cholangiocellular carcinoma (Sakai D et al., Abstract 615O).

Nasopharyngeal and Oropharyngeal Cancers

• KEYNOTE-048: the combination therapy with pembrolizumab improves overall survival in ENT tumors with PD-L1 expression ≥1% (Burtness B et al., Abstract LBA8_PR).
• Cisplatin remains the standard treatment for HPV-positive low-risk oropharyngeal cancer (Mehanna H et al., Abstract LBA9_PR).

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Colon Carcinoma/Colorectal Carcinoma

• An analysis of circulating tumor DNA detects minimal residual disease in stage II colorectal carcinoma (Reinert T et al., Abstract 456PD).
• VALENTINO study: a biomarker panel detects rare mutations that confer resistance to anti-EGFR therapy (Morano F et al., Abstract LBA22).
• CheckMate-142 demonstrates an overall response rate of 60% with nivolumab/ipilimumab in MSI-high mCRC (Lenz HJ et al., Abstract LBA18_PR).
• Neoadjuvant nivolumab/ipilimumab demonstrates impressive results in early colon carcinoma (Chalabi M et al., Abstract LBA37).
• MODUL shows no benefit of addition of atezolizumab to 5-FU/bevacizumab in first-line maintenance therapy (Grothey A et al., Abstract LBA19).
• VOLFI demonstrates excellent response rates for first-line therapy consisting of FOLFOXIRI/panitumumab in RAS wild type patients, but no benefit in progression free survival (Geissler M et al., Abstract 453PD).
• TRIBE2: Combination of triplet chemotherapy/antibodies in first line improves 2-year progression free survival and remains the standard of care for fit patients (Cremolini C et al., Abstract LBA20).

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Hepatocellular Carcinoma

• Phase-Ib trial: Atezolizumab plus bevacizumab facilitates a 77% disease control rate in patients with hepatocellular carcinoma (Pishvaian MJ et al., Abstract LBA26).

Gastric Cancer

• TAS-102, as the third line of therapy in advanced gastric cancer, improves overall survival by two months in third line for patients with gastric cancer (Arkenau H-T et al., Abstract LBA25).

Melanoma

• CheckMate-067: The 4-year follow-up data demonstrate marked benefit for patients with nivolumab/ipilimumab, also in the group of PD-L1 high tumors (Hodi F et al., Abstract LBA44).
• CheckMate-511 shows improved toxicity of a reduced dosing scheme of ipilimumab combined with standard nivolumab dose, at equal efficacy (Lebbé C et al., Abstract LBA47).
• A phase-II trial demonstrates low response rate (11%) of nivolumab/ipilimumab in patients with metastatic uveal melanoma (Piulats Rodriguez JM et al., Abstract 1247 PD).
• COMBI-Ad: The 4-year follow-up data of adjuvant dabrafenib/trametinib show a continued advantage over placebo (Long G et al., Abstract LBA43).
• OpACIN-neo confirms the high response rate with neoadjuvant nivolumab/ipilimumab. The toxicity with the new dosing regimen is lower than in the prior OpACIN (Rozeman E et al., Abstract LBA42).
• Phase-Ib/II: The combination of the intratumoral TLR9 agonist SD101/Pembrolizumab shows activity in anti-PD-1 treatment naïve patients with advanced melanoma (Long G et al., Abstract LBA45).
• Phase-I/II: The TLR9 agonist tilsotolimod/ipilimumab also shows interesting signals in metastatic melanoma refractory to PD-1 inhibition (Diab A et al., Abstract 1245PD).

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Renal Cell Carcinoma

• JAVELIN Renal 101: Avelumab/axitinib improves the progression-free survival vs. sunitinib, and will probably become the standard of care in first-line therapy of RCC (Motzer RJ et al., Abstract LBA6_PR).
• Gene-signatures of angiogenesis and immuno-oncology might help to select patients for first-line metastatic RCC treatment with either atezolizumab/bevacizumab or sunitinib in the IMmotion150 trial (Rini B et al., Abstract LBA31_PR)

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Lung Cancer

• A small trial (33 pts) shows that the combination of neoadjuvant nivolumab and ipilimumab or nivolumab alone have similar outcomes in resectable NSCLC, with around 25% of major pathological response. However, tumors from the combination arm showed a higher rate of infiltrating T cells (Cascone T et al., Abstract LBA49).
• An update of the ALTA-1L trial demonstrates superiority of brigatinib vs. crizotinib in intracranial response in patients with ALK-positive NSCLC and brain metastases. Newly developing brain metastases can be reduced by 50% with brigatinib compared to crizotinib (Popat S et al., Abstract LBA58).
• A subgroup analysis of the ALEX trial comparing the new generation ALK TKI alectinib to crizotinib, showed that patients with all EML4-ALK variants tend to have a better outcomes with alectinib (Dziadziuszko R et al., Abstract 1379PD).
• A phase-I trial shows that high GI toxicity of the ALK TKI ceritinib can be improved by reducing the dosage, with no reduction of efficacy (Cho BC et al., Abstract LBA59).
• Preliminary data of the phase-III study FLAURA shows that in EGFR-positive NSCLC, a significant proportion (around 15%) of patients treated with osimertinib develop MET amplification or modification, or a EGFR C797S mutation (around 7%) (Ramalingam SS et al., Abstract LBA50).
• The AURA-3 trial that compared osimertinib to chemotherapy in patients refractory to EGFR TKIs harboring the T790M mutation, generally supports the results of the FLAURA study, reveiling that amplifications of MET, HER2, and PIK3CA, or normally rare mutations in BRAF, KRAS and PIK3CA play a role in the resistance to osimertinib (Papadimitrakopoulou VA et al., Abstract LBA51).
• The phase-II trial GEOMETRY shows that the MET inhibitor capmatinib is active in patients with high-level MET amplifications or Exon 14 MET mutations (Wolf J et al., Abstract LBA52)
• A phase-II study combining the MET inhibitor tepotinib with gefitinib, shows good results in a subgroup of patients with high-level MET amplifications and MET protein overexpression compared to standard chemotherapy (Cheng Y et al., Abstract 1377O).
• An update of the phase-II trial PACIFIC in patients with irresectable stage III NSCLC receiving combined radiochemotherapy followed by either durvalumab or placebo found that durvalumab efficacy (progression free survival, overall survival, and overall response rate) is not related to the time to durvalumab treatment after completion of radiochemotherapy (Faivre-Finn C et al., Abstract 1363O).
• A small randomized phase-II trial in patients with refractory small-cell lung cancer showed that atezolizumab monotherapy shows inferior ORR compared to standard chemotherapy (Pujol J-L et al., Abstract 1664O).
• The SAKK1512 trial implicates that early prophylactic cranial irradiation in patients with limited disease SCLC does not improve neurocognitive function compared to a sequential regimen (Vees H et al., Abstract 1667PD).
• SPLENDOUR study: the RANKL inhibitor denosumab given in combination with standard first-line platinum-based chemotherapy does not improve the OS of patients with advanced NSCLC (Peters S et al., Abstract 1385PD).

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Ovarian Cancer

• SOLO-1 olaparib in the front-line maintenance setting sets a new standard in BRCA-mutated ovarian cancer (Moore K et al., Abstract LBA7_PR). The duration of maintenance therapy was 2 years in the SOLO-1 trial, the optimal duration is not yet clear. The PAOLA trial investigates olaparib/bevacizumab after completion of primary therapy also in BRCA wild type patients. The combination of a PARP inhibitor plus anti-angiogenic therapy might be promising (NCT02477644 bzw. AGO-Ovar 20).
• HIPEC: Die Datenlage ist dünn und die Anwendung derzeit nur in Studien gerechtfertigt (Controversy Session, HIPEC: Is there a role in ovarian cancer?).
• Studie 221 zeigt einen PFS-Vorteil durch zusätzliches peg. liposomales Doxorubicin nach platinsensitivem Rezidiv (Pfisterer J et al., Abstract 933O).

Prostate Cancer

• GETUG-12: Adding docetaxel/estramustin in high risk, localized prostate cancer does not confer an overall survival advantage (Fizazi K et al., Abstract 791O).
• STAMPEDE: Abiraterone plus predniso(lo)ne improves overall survival in hormone-sensitive metastatic low-risk prostate cancer (Hoyle AP et al., Abstract LBA4).
• ERA 223: The combination of radium-223/abiraterone/predniso(lo)ne should not be used in asymptotic, chemotherapy-naïve castration-resistant prostate cancer with prevalent bone metastasis (Smith M et al., Abstract LBA30).
• STAMPEDE: Patients with oligometastatic disease and low metastatic burden have a clear advantage of additional localized irradiation of the prostate (Parker C et al., Abstract LBA5_PR).

Sarcoma

• The survival advantage for patients with sarcomas treated in reference centers was confirmed (Blay Y et al., Abstract 1601O; Smolle M et al, Abstract 1602O).
• Nanoparticles activated by radiotherapy increase the rate of complete remissions in locally advanced soft tissue sarcoma (Bonvalot S et al., Abstract LBA66).
• The novel tyrosine kinase inhibitor DDC-2618 is efficient in second, third, and fourth-line of therapy in gastrointestinal stroma tumours (George S et al., Abstract 1603O).
• A phase-II trial demonstrates the efficacy of cabozantinib, especially in heavily pretreated Ewing sarcomas (Italiano A et al., Abstract LBA67).

CNS Metastasis and Glioma

• Recurrent CNS metastases of NSCLC are often similar to the initial metastasis with respect to mutational burden and immune cell infiltration (Berghoff AS et al., Abstract 372O).
• Intrathecal therapy of cytarabine improves progression-free survival of breast cancer with leptomeningeal carcinomatosis (Le Rhun E et al., Abstract 371O).
• Glioma: Mismatch repair deficiency, a predictive marker for immunotherapy, is highly prevalent in recurrent gliomas (Lombardi G et al., Abstract 374O).

Quelle: ESMO 2018