EGFR mutations cause inconsistent response to EGFR tyrosine-kinase inhibitors (TKI). To better understand these features, we reviewed all cases of EGFR-mutated non-small-cell lung cancer collected in ...the Biomarkers France database.
Of 17664 patients, 1837 (11%) with EGFR-mutated non-small-cell lung cancer were retrospectively analyzed for clinical and molecular characteristics. Results were correlated with survival and treatment response for the 848 stage IV patients.
EGFR exon 18, 19, 20 and 21 mutations were found in 102 (5.5%), 931 (51%), 102 (5.5%) and 702 (38%) patients, respectively. Over 50% of exon 18 and 20 mutated patients were smokers. The median follow-up was 51.7months. EGFR mutation type was prognostic of overall survival (OS) versus wild-type {exon 19: hazard ratio (HR)=0.51 95% confidence interval (CI): 0.41–0.64, P < 0.0001; exon 21: HR= 0.76 (95% CI: 0.61–0.95), P = 0.002; exon 20: HR= 1.56 (95% CI: 1.02–2.38), P = 0.004}. EGFR mutation type was prognostic of progression-free survival versus wild-type exon 19: HR= 0.62 (95% CI: 0.49–0.78), P < 0.0001; exon 20: HR= 1.46 (95% CI: 0.96–2.21), P = 0.07. First-line treatment choice did not influence OS in multivariate analysis. First-line TKI predicted improved progression-free survival versus chemotherapy HR= 0.67 (95% CI: 0.53–0.85), P = 0.001. OS was longer for del19 versus L858R, which was associated with better OS compared with other exon 21 mutations, including L861Q. TKI improved survival in patients with exon 18 mutations, while chemotherapy was more beneficial for exon 20-mutated patients.
EGFR mutation type can inform the most appropriate treatment. Therapeutic schedule had no impact on OS in our study, although TKI should be prescribed in first-line considering the risk of missing the opportunity to use this treatment.
Background: Taxotere® (docetaxel) at the dose of 75 mg/m2 every 3 weeks is a standard therapy for pretreated non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the safety ...profile of two schedules of docetaxel administration (every 3 weeks versus weekly) in patients with pretreated NSCLC. Patients and methods: From February 2000 to February 2001, 125 patients with locally advanced or metastatic NSCLC were randomised after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m2 administered every 3 weeks (Dq3w) or docetaxel 40 mg/m2 given weekly for 6 weeks followed by 2 weeks of rest (Dqw). Safety evaluations focused on grade 3–4 neutropenia, febrile neutropenia, nausea-vomiting and asthenia. Results: Patients' characteristics were well balanced between arms. The most common National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3–4 toxicity was neutropenia, which occurred in 48.4% of Dq3w patients versus 15.9% of Dqw patients (P=0.001). In addition, febrile neutropenia were observed in 6.5% of patients in Dq3w versus 0% in Dqw. Grade 3–4 asthenia was more frequent in Dqw. Other non-haematological toxicities were very rare. Regarding efficacy, there was a trend towards a better disease control rate in Dq3w: 32.2% versus 25.4% in Dqw. Median time to progression and survival were rather similar in both arms, respectively: 2.1 months (range 2–3.2) and 5.8 months (range 4.0–7.0) in Dq3w and 1.8 months (range 1.6–2.3) and 5.5 months (range 3.7–6.6) in Dqw. Conclusions: While both schedules had a favourable safety profile, a significant lower rate of severe neutropenia was observed in the weekly arm. Both regimens had similar efficacy. The weekly regimen could be considered as a good alternative for patients at risk of severe neutropenia.
Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours.
We assessed EGFR and KRAS by direct sequencing in 154 ...patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies.
Thirteen of 36 exon 19 EGFR-mutated tumours (36%)—including 12 of 22 with p.Glu746_Ala750del (55%)—were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)—including 4 of 17 with p.Leu858Arg (24%)—were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements—including two of three with ELM4-ALK fusion transcripts—were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4.
Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.
To describe the main characteristics and the treatment of cryptococcosis in patients with sarcoidosis.
Multicenter study including all patients notified at the French National Reference Center for ...Invasive Mycoses and Antifungals.
Retrospective chart review. Each case was compared with two controls without opportunistic infections.
Eighteen cases of cryptococcosis complicating sarcoidosis were analyzed (13 men and 5 women). With 2749 cases of cryptococcosis registered in France during the inclusion period of this study, sarcoidosis accounted for 0.6% of all the cryptococcosis patients and for 2.9% of the cryptococcosis HIV-seronegative patients. Cryptococcosis and sarcoidosis were diagnosed concomitantly in four cases; while sarcoidosis was previously known in 14/18 patients, including 12 patients (67%) treated with steroids. The median rate of CD4 T cells was 145 per mm(3) (range: 55-1300) and not related to steroid treatment. Thirteen patients had cryptococcal meningitis (72%), three osteoarticular (17%) and four disseminated infections (22%). Sixteen patients (89%) presented a complete response to antifungal therapy. After a mean follow-up of 6 years, no death was attributable to cryptococcosis. Extra-thoracic sarcoidosis and steroids were independent risk factors of cryptococcosis in a logistic regression model adjusted with the sex of the patients.
Cryptococcosis is a significant opportunistic infection during extra-thoracic sarcoidosis, which occurs in one-third of the cases in patients without any treatment; it is not associated to severe CD4 lymphocytopenia and has a good prognosis.
Mycobacterium simiae pulmonary infections remain exceptional in France.
We report a case of M. simiae lung infection and a 10-year follow-up in a non-immunocompromised host.
This case emphasizes the ...difficulties of choosing the appropriate drugs and their side effects in the absence of any existing gold standard.
Polymyalgia rheumatica is an inflammatory condition belonging to the connective tissue diseases, which occurs quite frequently in the elderly. Previously, cases have been reported in association with ...malignant tumours, in a synchronous fashion or prior to the appearance of the cancer. In these cases, the polymyalgia rheumatica is considered to be a paraneoplastic syndrome. We report the cases of a 63-year-old woman and a 58-year-old man with severe proximal girdle pain associated to a high-level of systemic inflammatory markers and a diagnosis of polymyalgia rheumatica was made. In the face of a lack of ineffectiveness of analgesic and anti-inflammatory treatments, an intensive investigation was undertaken which in both cases revealed an adenocarcinoma of the lung. The rheumatic manifestations responded well to chemotherapy targeting the lung tumour. We present here a review of the literature to give prominence to the diagnostic pitfalls that can occur around paraneoplastic polymyalgia rheumatica. The presence of therapeutic resistance at the onset of treatment and other atypical features may suggest the presence of an occult malignancy.
Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall ...survival (OS) of only 25% to 33%.
STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab 1 mg/kg, every three weeks (Q3W) plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint.
Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months 95% confidence interval (CI) 7.0-not estimable (NE) versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively.
The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.
•First randomised trial comparing nivolumab/ipilimumab versus observation after standard chemo-radiotherapy and PCI in LD-SCLC.•Period on active treatment was short with a median time to nivolumab/ipilimumab discontinuation <2 months.•No improvement for PFS and OS for immunotherapy consolidation over observation.•Higher OS benefit observed for patients on twice daily radiotherapy schedule (versus once daily), female sex and ECOG PS 1.
Malignant melanoma most commonly presents as a primary neoplasm of the skin, but has been described in other mucosal sites. Rarely, malignant melanomas have been reported as primary visceral ...neoplasms, including the lung. Most such lesions have been dismissed as metastases from undocumented or regressed primary cutaneous or ocular melanomas.
We report an original observation of an 82-year-old man with a pulmonary nodule presenting with chest pain. The diagnosis of melanoma was established on biopsies carried out under computerized tomography scanning and confirmed after right upper lobectomy two months later.
Melanomas of the respiratory tract are usually metastatic in origin and a primary melanoma in very rare. Strict criteria must be applied before a diagnosis of primary malignant melanoma of lower respiratory tract can be accepted. Melanoma may be confused with more conventional types of lung cancer and other pigmented tumours.
IFCT study administering 7.5 mg/kg Bevacizumab plus chemotherapy after chemotherapy induction did not improve outcomes in extensive SCLC patients.
This randomized phase II–III trial sought to ...evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC).
Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle.
In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months 95% confidence interval (CI) 4.9% to 6.0% versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers.
Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.
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