Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: 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%. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Small cell lung cancer and immuno-oncologic agents: End of the cisplatin - etoposide era?] / Cancer bronchique à petites cellules et agent onco-immunologique : peut-on sortir de l'ère du tout cisplatine étoposide ?

In the setting of small cell lung cancer (SCLC), the development of immuno-oncological agents, particularly those targeting Programmed cell Death protein 1 (PD-1) and Programmed cell Death protein Ligand 1 (PD-L1), is still at an early stage. Two critical elements need to be considered : the current data are extracted from Phase I and Phase II trials and the level of evidence from phase III trials has not been reached as it has been for non-small cell lung cancer (NSCLC) or for malignant melanoma ; The second aspect is the slow development of predictive factors for response to the immuno-oncological agents targeting the PD-1 receptor and its ligand. The clinical data are still too fragmentary to produce recommendations, although the improvement in progression-free survival seen in different phase II studies is promising. The expectation of clinicians dealing withSCLC is an indication of the challenge that this disease currently poses to oncology and justifies a focused clinical research effort.

[What do chemotherapy specialists expect of lung cancer?] / Qu'attendent les médecins spécialistes de la chimiothérapie des cancers du poumon ?

OBJECTIVE: In an attempt to understand physicians' expectations of chemotherapy, a group of lung cancer specialists was involved in an online survey investigating their opinions by a self-questionnaire. The questionnaire described five different chemotherapy prescription situations for lung cancer patients (stages IIIB or IV). METHOD: A total of 30 expert specialists were invited; 22 responded (73%). For each of the clinical situations, the expert was asked for his opinion on 3 items: cure, prolongation of survival and alleviation of symptoms. Each item was judged on a Likert scale with categories between -2 "not at all probable" and +2 "quite likely". RESULTS: For "cure", the percentage of -2 responses differed significantly according to the clinical situation (Fisher test: P<0.00001). The trend test showed a relationship between the percentage of -2 responses and the suspected order of the clinical situations (Cochran-Armitage trend test: P<0.0001). For symptom alleviation, the percentage of responses +2 and +1 differed significantly according to the clinical situation (Fisher test: P=0.00013, trend test: P<0.0001). CONCLUSION: What specialist physicians expect of chemotherapy in terms of curability and symptom relief differs according to the actual statistical prognosis of each situation as presented in the literature. The worst prognostic situation leads to the strongest expectation in terms of symptom relief and, conversely, the lowest for curability.

Imaging of postoperative complications following surgery for lung cancer.

The complications following surgery for lung cancer vary depending upon the comorbidities and the type of surgery. Hemorrhage, infections and pulmonary edemas are not specific to the type of resection but frequently occur following pneumonectomies. Morbidity following pneumonectomies is related to the significant changes in the contents of the intrathoracic space. Pulmonary infarction and torsion are emergency situations that develop following lobectomy. CT shows features of localized congestion and stenosis or occlusion of a vein or bronchus. Rapid identification of severe events, in particular by systematic CT is essential for appropriate management of a postoperative or delayed complication of lung cancer surgery.

Normal postoperative appearances of lung cancer.

The major lung resections are the pneumonectomies and lobectomies. The sublobar resections are segmentectomies and wedge resections. These are performed either through open surgery through a thoracotomy or by video-assisted mini-invasive surgery for lobectomies and sublobar resections. Understanding the procedures involved allows the normal postoperative appearances to be interpreted and these normal anatomical changes to be distinguished from potential postoperative complications. Surgery results in a more or less extensive physiological adaptation of the chest cavity depending on the lung volume, which has been resected. This adaptation evolves during the initial months postoperatively. Chest radiography and computed tomography can show narrowing of the intercostal spaces, a rise of the diaphragm and shift of the mediastinum on the side concerned following major resections.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.

BACKGROUND: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials.

OBJECTIVES: Two phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500mg/m(2) plus cisplatin 75mg/m(2) every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. METHODS: Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. RESULTS: Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. CONCLUSIONS: The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.

[One more word about the diagnostic. A metapsychological approach]. / Encore un mot sur l'annonce Une approche métapsychologique.

Nearly a decade since the first experiment in France of the so-called "announcement policy" a concerted effort, the pooling of skills of health professionals from different backgrounds, have had noticeable positive effects on the daily practice. This article attempts at analyzing the question that was causing the application of former patients and their main complaint: the lack of communication and its direct consequences, anguish and loneliness. Subsequently, the announcement policy, this multifaceted approach, had consisted of creating for the patient what can be called "a good enough environment able to hold". It is therefore not a plan but a disposal (if we are willing to agree on the fact that these are the qualities of the therapeutic setting that count and not the format by itself). Considering the ipseity of each patient, the uniqueness of each particular situation, of each social background, the need for harmonization of the announcement policy is questionable. Harmonization does not mean uniformity. The quality of this policy must be adapted closer to each case. However, it must be based on the basic principles and might also take into account the dimension of anguish. These fundamental principles are directly derived from the principles of medical humanism, those that have brought meaning to scientific progress.

[Specificity of the psychological undertaking of a patient in thoracic oncology]. / Spécificité de la prise en charge psychologique en oncologie thoracique.

The question raised by the title calls for a balanced answer. As a matter of fact, like in many clinical situations in which an illness threatens the patient's survival, the singularity of each case makes any attempt of generalization simplistic. Writing about the speficity of the psychological undertaking in thoracic oncology has to avoid two pitfalls: denying any psychosociological specificity of thoracic cancerology, and thus not providing the reader's understanding with anything which could help them read the most frequent problematics. And secondly turn clinical qualitative data into generalities stuck on each case, and rejecting the singularity of the sick person as a subject. As we attempt to avoid both traps, the three next points will be tackled: the announcement of cancer is prototypical of a trauma, and calls up an intense affect of anguish. This affect can be read through social representations, which intervene within the exchange doctor - sick person. The subjectivation of this relation cannot be understood without taking the environment into account, and especially what the affected person knows about cancer owing to their belonging to a socius. In the traumatic atmosphere thus created, the rereading of the phenomenons - cropping up between a somatic symptom experienced by the patient and a traumatic language revolving around the compulsory term "cancer" - is achieved according recurrent thematic lines. As we do not wish to reach the exhaustiveness of the significant unities, neither their reassembly, we will limit ourselves to the development of one main line: that of the relation to time, to temporality, and to presentism.

Third CECOG consensus on the systemic treatment of non-small-cell lung cancer.

The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic options.

[Diagnostic. Announcing cancer. From concept to practice]. / Le dispositif d'annonce. Du concept à la pratique.

Communicating in oncology belongs to communicate in difficult circumstances. Moreover, "to say" is a medical requirement. We need to make this communication a field of realistic proposals and proceed step by step. This is probably one of the greatest challenges that we have to face in oncology. Organizing first medical consultation in oncology might offer an opportunity to speak with patient of any possible issues. In doing so, give it the means to fight and it is also accompany him. Accompanying this is not a palliative, not a "lack of...". This is the noble part of our work that can not be reduced to the technique.

[The Delivery of the message, from concept to practice]. / Le dispositif d'annonce, du concept à la pratique.

Communication in oncology often means communicating in difficult circumstances. Moreover, "to tell" is an essential requirement in medicine. We need to make this communication a series of realistic proposals and proceed step by step. This is probably one of the greatest challenges that we have to face in oncology. The Delivery of the message consists of using the first consultation as an opportunity to speak of what is possible. In so doing we present the patient with the means to fight the disease and also give him support. Support is not palliative, not a "lack of...", but a vital part of our work that can not be reduced to a technique.

Quality of life and comorbidity score as prognostic determinants in non-small-cell lung cancer patients.

BACKGROUND: Both quality of life (QoL) and comorbidity influence therapy and prognosis of non-small-cell lung cancer (NSCLC). We previously developed a lung cancer disease-specific simplified comorbidity score (SCS) and demonstrated the prognostic impact of this disease-specific instrument. This study aimed at validating the SCS in a prospective bicentric NSCLC population by measuring its relative prognostic determinant impact taking into account well-established variables such as QoL, performance status (PS), Charlson comorbidity index (CCI) and disease stage. PATIENTS AND METHODS: Prognostic values of different pretherapeutic features were tested in univariate and multivariate analyses in a population of 301 NSCLC. RESULTS: Median survival was 17 months. One-third of patients reporting difficulties in their normal daily activities and an overall poor QoL. The following pretreament variables were independent determinants of a shorter overall survival: advanced disease, SCS, Lung Cancer Symptoms Scale global symptoms score, anaemia, hyponatremia, serum alkaline phosphatases level, serum CYFRA 21-1 and serum neuron-specific enolase. CONCLUSION: In this extended validation population, the SCS is more informative than the CCI in predicting NSCLC patient outcome as the former is also more disease specific. Combination of both SCS comorbidity score and LSCC QoL yields a more accurate information that conventional analysis of PS.

[Smoking cessation in patients with lung cancer]. / Indications et méthodes d'aide au sevrage tabagique chez un patient fumeur atteint de cancer bronchique.

Smoking cessation is an important part of the management of patients with lung cancer. Continued smoking has been found to diminish treatment efficacy, to exacerbate side effects and to have a detrimental effect on survival. Smoking increases postoperative pulmonary complications and tolerance and efficacy of medical treatment (chemotherapy, targeted therapy, radiotherapy) are diminished. Moreover, the quality of life of current smokers is lower and the risk of a second primary malignancy is increased. Hospitalization is a good opportunity to propose smoking cessation. Clinical practice guidelines recommend the use of combined behavioral and pharmacological therapies. The efficacy of smoking cessation programs for cancer patients has been demonstrated. There is a clear dose-response relationship between number of contacts, intensity level of person-to-person contact and total amount of contact time. Multidisciplinary approaches increase abstinence rates. First line phamacotherapies (nicotine replacement therapy and sustained-release antidepressant bupropion) have been found to be safe and effective. Varenicline is a new drug for smoking cessation but it remains to be evaluated in oncology patients.