1b) Be sure to check out (and earn even MORE ?CE/#CME credit from my colleague @PatelOncology 's introduction to contemporary #ES_SCLC management at https://t.co/hqEQbEqvBg.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
We strive to keep our ? med colleagues up to date on oncology issues!
3) This program is supported by an educational grant from AstraZeneca and is intended for #healthcare providers. Statement of accreditation and faculty disclosures are at https://t.co/0EkFYk4TZx pic.twitter.com/G4FGuBgSzy
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
4b) @ESMO guidelines ? https://t.co/aUvjNS1Pcb
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
recommend CT-scan and brain imaging. 18-FDG-PET is optional unless bone metastases are suspected. pic.twitter.com/CMOFsFst9d
5a) What is the current standard-of-care for 1L tx of pts with ES-SCLC?
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
a. chemotherapy w/platinum & #etoposide
b. chemotherapy w/platinum & etoposide combined w/ immune checkpoint inhibitor
c. chemotherapy w/platinum & etoposide followed by immune checkpoint inhibitor
5c) All recommend immune checkpoint inhibitors #atezolizumab or #durvalumab to be combined with chemotherapy with platinum and #etoposide upfront, with a high level of evidence and recommendation.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
❓So now: is your preference for carboplatine or cisplatine?
5e) From this meta-analysis, it seems that in younger patients (<70 years), the outcome might be moderately better with cisplatin, although these subgroup analyses were exploratory.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
5g) Therefore, @ESMO guidelines ? https://t.co/aUvjNS1Pcb state that #cisplatin can be substituted by #carboplatin.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
6b) The answer is 4 cycles, then maintenance w/ immunotherapy
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
All guidelines primarily recommend immune checkpoint inhibitors atezolizumab or durvalumab to be combined w/ chemotherapy w/ platinum and etoposide upfront for 4 cycles. @NCCN guidelines ? https://t.co/8LDqdMhluz
7) These recs are based on 2 landmark phase III #RCTs that demonstrated an #OS benefit with combination of chemotherapy and immunotherapy: #IMpower_133 ? https://t.co/SER3XNl2r7
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
and #CASPIAN ? https://t.co/b9CwOV2lWd
8b) In #IMpower 133, OS benefit was observed with atezolizumab, with median OS of 12.3 months vs. 10.3 months with placebo. pic.twitter.com/IYHgPIvoR9
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
9b) In #CASPIAN, OS benefit was observed with median OS of 10.5 in the control arm and 12.9 months in the durvalumab arm. #Durvalumab led to sustained benefit with 3 year OS rate of 17.6% vs. 5.8% in the control arm. pic.twitter.com/AXNHvBJ8D2
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
11) Another randomized trial, conducted in Asia, showed a similar benefit with other anti-#PD1 agents in trials with comparable designs: #ASTRUM_005 with #serplulimab https://t.co/RqLbS6f7g1 pic.twitter.com/RIulgszUTc
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
13) In clinical practice, patients may not be amenable upfront to #immunotherapy, because of #brain_metastases, poor PS, or need for high steroid doses. #Chemotherapy alone may then be delivered.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
15) Meanwhile, we must initiate immunotherapy during chemotherapy. #CheckMate_451 failed to show any benefit of #ICIs nivolumab+/-ipilimumab as switch maintenance when initiated in non-progressive #SCLC after 4 cycles of platinum & etoposide. ? https://t.co/l5ebGc2TU9
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
16b) @NCCN guidelines ? https://t.co/8LDqdMhluz recommend for #ES_SCLC that during systemic therapy, response assessment by chest/abdomen/pelvis CT with contrast should occur after every 2–3 cycles of systemic therapy and at completion of therapy.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
17a) Is there any predictor for the efficacy of immunotherapy that would help to select patients and identify the long-term responders?
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
17c) From #CASPIAN, an analysis was done in long-term responders ≥12 months ? https://t.co/TC9oGeFPxz pic.twitter.com/gFFZQRb7To
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
18) OK, need a break? Lots of info shared already, but please return TOMORROW for more on management of #ES_SCLC!
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
?@PatelOncology @StephenVLiu @oncologician @LealTiciana @chulkimMD @Tony_Calles @FawziAbuRous @NickMarcouxMD @NReguart @ADesaiMD#LCSM #FOAMed
20a) A molecular classification of #SCLC has emerged, based on #RNA-Sequencing signature, and defining 4 groups of tumors, referred as to #ASCL1 (SCLC-A), #NEUROD1 (SCLC-N), #POU2F3 (SCLC-P), #Inflamed (SCLC-I), and possibly #YAP1 (SCLC-Y).
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
?? https://t.co/6hlsDsneR9
21) Emerging evidence suggest that the #SCLC_I is consistently associated with more prolonged survival with chemotherapy and immune checkpoint inhibitor, based on data from #Impower_133 and #CASPIAN
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
? https://t.co/s7xv9QH7a3
? https://t.co/AkCWCdClRm pic.twitter.com/ffExqzejME
22b) In patients with #ES_SCLC that has responded to systemic therapy, #PCI decreases brain metastases. A randomized trial conducted by the #EORTC found improved overall survival with PCI.
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
? https://t.co/TjuhUv4R9X
22d) @NCCN guidelines ? https://t.co/8LDqdMhluz recommend MRI surveillance and consider #PCI as an option pic.twitter.com/C2qBZhTnvT
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
23b) Per @NCCN guidelines ? https://t.co/8LDqdMhluz and @ESMO guidelines ? https://t.co/aUvjNS1Pcb, consider thoracic RT in patients with good response to #ES_SCLC pic.twitter.com/1OKnVrJ8ea
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
24b) Likelihood of response is highly dependent on the time from initial therapy to relapse. If this interval is 6 months or less (refractory or resistant disease), response to most agents or regimens is poor (≤10%).
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
24d) Note that the cut-off is 6⃣months per @NCCN guidelines: ? https://t.co/8LDqdMhluz
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
…
but 3⃣ months per @ESMO guidelines https://t.co/aUvjNS1Pcb
25b) In platinum-refractory tumors or after rechallenge in sensitive tumors, multiple options are listed in the @NCCN guidelines ? https://t.co/8LDqdMhluz and @ESMO guidelines ? https://t.co/aUvjNS1Pcb pic.twitter.com/gugzKUYR7v
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
26b) Oral administration is usually preferred at a dose of 2.3 mg/m2/d on days 1 – 5 every 21 days according to marrow recovery.
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
The @NCCN #SCLC Panel recommends topotecan as a preferred subsequent therapy option for pts with SCLC who have relapsed 6 months or less after therapy.
27b) However, in the randomized #ATLANTIS trial, #lurbinectedin combined with #doxorubicin did not show a significantly better survival than #topotecan. See https://t.co/YIjU6KCupe pic.twitter.com/3dyjfX75Vz
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
28a) A promising strategy is #tarlatamab, a bispecific T-cell engager agent targeting #DLL_3, a cell surface receptor of #SCLC cell and #CD3, that reported 23% overall response rate in the #DELLPHI_300 phase I trial presented at #WCLC 2022 meeting.
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
28c) Adverse events include #cytokine_release_syndrome, neurologic events, and #neutropenia. pic.twitter.com/f0E6lRRgV2
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
29) Another strategy assessed in clinical trials is B7 homologue 3 (#B7_H3) targeting. In a phase I study, DS-7300 (B7-H3 deruxtecan Antibody Drug Conjugate #ADC) showed promising effect in patients with relapsed/refractory SCLC. These data were presented at #ESMO22 meeting. pic.twitter.com/3yt7fz8KBZ
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
30b)
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
? Second-line consists of chemotherapy rechallenge in platinum-sensitive cases, or #topotecan/#lurbinectedin as preferred options in platinum-resistant cases
31) And you made it! You just earned 0.75h ?CE/#CME from your ONLY source for #accredited serialized #tweetorials. ?️ to https://t.co/B51azskI6f for your certificate! I am @nicogirardcurie. FOLLOW US!
— pulmmed_ce (@Pulmmed_CE) February 9, 2023