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Page 10 of 13 Abughanimeh et al. J Cancer Metastasis Treat 2020;6:50 I http://dx.doi.org/10.20517/2394-4722.2020.110

Table 3. Clinical trials of targeted therapies in the setting of recurrent/relapsed SCLC
Agent Study design Overall response Progression free Overall survival Median duration of
survival response
Alisertib Phase II, single arm 2nd or 3rd line in 21% 2.1 months Not reported 4.1 months
different solid malignancies including
SCLC [59]
Veliparib Phase II, veliparib + TMZ to TMZ + 39% vs. 14 (P-value = 3.8 months vs. 2 8.2 months vs. 7 4.61 months vs. 3.68
placebo 2nd line [27] . 0.016) months (P = 0.39) months (P = 0.5) months (P = 0.0507)
Pazopanib Phase II, single arm 2nd line [61] 13.8% PR 2.5 months 6 months Not reported
Anlotinib Phase II anlotinib vs. placebo as ≥ DCR: 71.6% vs. 13.2% 4.1 months vs. 0.7 7.3 months vs. 4.9 Not reported
3rd line [62,63] . (P-value < 0.0001) months months
SCLC: small cell lung cancer; TMZ: Temozolomide; DCR: disease control rate; PR: partial response

Table 4. Active clinical trials evaluating new treatments for recurrent/relapsed SCLC
Study name/ClinicalTrials.gov ID Study design Treatment arms Primary outcome
ATLANTIS/NCT02566993 Phase III Lurbinectedin + doxorubicin vs. CAV vs. topotecan Overall survival
CheckMate 331/NCT02481830 Phase III Nivolumab vs. topotecan vs. amrubicin as 2nd line Overall survival
TAHOE/NCT03061812 Phase III Rovalpituzumab vs. topotecan as 2nd line Overall survival
KEYNOTE-158/NCT02628067 Phase II Pembrolizumab as 2nd line Overall response rate
MCC-19163/NCT03406715 Phase II Single arm: Ipilimumab + Nivolumab + Dendritic Disease control rate
Cell Based p53 Vaccine as a 2nd line and beyond
AFT-17/NCT02963090 Phase II Topotecan IV vs. Pembrolizumab as 2nd line Progression free survival
CA001-030/NCT02247349 Phase I/II BMS-986012 + nivolumab vs. BMS-986012 alone Safety as measured by
as 2nd line frequency of adverse events.
KEYNOTE-028/NCT02054806 Phase I Pembrolizumab as 2nd line in different solid tumors Overall response rate
MEDIOLA/NCT02734004 Phase I/II Olaparib + bevacizumab + durvalumab vs. Olaparib Disease control rate, safety and
+ durvalumab as 2nd line and beyond tolerability of the drugs, overall
response rate.

SCLC: small cell lung cancer; CAV: Cyclophosphamide, Doxorubicin, and Vincristine

Table 4 summarizes some of the ongoing clinical trials to investigate new approaches for relapsed/refractory
SCLC.

EFFECT OF COVID-19 ON SCLC TREATMENT
In late 2019, multiple cases of atypical pneumonia had been reported in Wuhan, China, caused by a novel
type of coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that led to
[64]
the COVID-19 disease . So far, its impact on lung cancer diagnosis and treatment is not well reported.
However, a recent study from Spain did show that patients with lung cancer and COVID-19 infection
[61]
have a higher mortality rate compared to the general population with COIVD-19 alone . While there is a
concern that treating these patients may increase the risk of complications associated with the SRA-CoV-2,
relapsed SCLC has a very aggressive course. We recommend continuing treatment of these patients while
monitoring for the development of COVID-19 disease.

CONCLUSION
In conclusion, relapsed SCLC remains a difficult disease with a dismal prognosis. Most of the patients will
have disease relapse after a few months of first-line treatment. Till date, there are only 2 drugs approved
by the FDA, topotecan and lurbinectedin both with modest efficacy. However, the recent advances in
immunotherapy and targeted therapy are exciting, and the results of ongoing trials may help find a strategy
that will improve outcomes for these patients.

DECLARATIONS
Authors’ contributions
Wrote the manuscript: Abughanimeh O